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  1. Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

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    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2015-12-01

    Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

  2. IL6 and IL10 are genetic susceptibility factors of periodontal disease

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    Luca Scapoli

    2012-01-01

    Conclusions: The present investigation indicated that polymorphisms of IL6 and IL10 constitute risk factors for chronic periodontitis, while there was no evidence implicating a specific IL1A or IL1B genotype.

  3. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1 Virus Infection in the Mexican Population.

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    Román Alejandro García-Ramírez

    Full Text Available Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1 virus infections. Most patients infected with the influenza A (H1N1 pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α. We propose that single-nucleotide polymorphisms (SNPs in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1 pdm09 virus infection.145 patients with influenza A (H1N1 (pA/H1N1, 133 patients with influenza-like illness (ILI, and 360 asymptomatic healthy contacts (AHCs were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8 using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4 were measured on a Luminex 100.The IL6 rs1818879 (GA heterozygous genotype was associated with severe influenza A (H1N1 virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05-11.56, and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively. Genetic susceptibility was determined (pA/H1N1 vs. AHC: the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9, and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89. Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007. Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001 and IL-6 (p  =  0.007 levels.The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1 virus

  4. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

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    García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

  5. IL-1b, IL-6 and IL-8 Levels in Gyneco-Obstetric Infections

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    Beatriz Basso

    2005-01-01

    Full Text Available Objective. During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1β, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy.

  6. Variation in the IL1B, TNF and IL6 genes and individual susceptibility to prosthetic joint infection

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    Stahelova Anna

    2012-05-01

    Full Text Available Abstract Background Prosthetic joint infection (PJI is an important failure mechanism of total joint arthroplasty (TJA. Here we examine whether the particular genetic variants can lead to increased susceptibility to PJI development. Results We conducted a genetic-association study to determine whether PJI could be associated with functional cytokine gene polymorphisms (CGP influencing on innate immunity response. A case–control design was utilized and previously published criteria for PJI were included to distinguish between cases and control subjects with/without TJA. Six single nucleotide polymorphisms (SNPs located in the genes for interleukin-1beta (SNP: IL1B-511, +3962, tumour necrosis factor alpha (TNF-308, -238 and interleukin-6 (IL6-174, nt565 were genotyped in 303 Caucasian (Czech patients with TJA (89 with PJI / 214 without PJI, and 168 unrelated healthy Czech individuals without TJA. The results showed that carriers of the less common IL1B−511*T allele were overrepresented in the group of TJA patients with PJI (69% in comparison with those that did not develop PJI (51%, p = 0.006, pcorr = 0.037 and with healthy controls (55%, p = 0.04, pcorr = N.S.. There was no significant difference in the distribution of the remaining five investigated CGPs and their haplotypes between groups. Conclusion A functional variant of the gene encoding for IL-1beta was preliminarily nominated as a genetic factor contributing to the susceptibility to PJI. Our results should be independently replicated; studies on the functional relevance of IL1B gene variants in PJI are also needed.

  7. Relationships of common polymorphisms in IL-6, IL-1A, and IL-1B genes with susceptibility to osteoarthritis: a meta-analysis.

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    Cai, Hao; Sun, Huan-Jian; Wang, You-Hua; Zhang, Zhe

    2015-08-01

    Observational and experimental studies have arrived at inconsistent conclusions about whether common polymorphisms in IL-6, IL-1A, and IL-1B genes are associated with an increased risk of osteoarthritis (OA). Therefore, we undertook a comprehensive meta-analysis to more systematically summarize the relationships of IL-6, IL-1A, and IL-1B genetic polymorphisms with susceptibility to OA. We screened the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases up to 31 March 2014. We used STATA software to analyze statistical data. Odds ratios (ORs) and their corresponding 95 % confidence intervals (95 % CIs) were calculated. Seventeen independent case-control studies were included in this meta-analysis with a total number of 7,491 subjects, comprised of 3,293 OA patients and 4,729 healthy controls. Our results indicate that IL-6, IL-1A, and IL-1B genetic polymorphisms are statistically correlated with an increased risk of OA under the allele and dominant models. According to a subgroup analysis based on disease, a higher frequency of IL-6 genetic polymorphisms was observed among knee OA and hand OA patients, but not among hip OA and DIP OA patients. A higher frequency of IL-1A genetic polymorphisms were found among hip OA patients, hand OA, hip OA and DIP OA patients. Furthermore, we observed a higher IL-1B polymorphism frequency among knee OA and hip OA patients, but not among hand OA patients. Our findings provide evidence that IL-6, IL-1A, and IL-1B genetic polymorphisms may be correlated with susceptibility to OA.

  8. Serum IL-6 and IL-10 concentrations in bitches with pyometra undergoing ovariohysterectomy.

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    Dąbrowski, Roman; Pastor, Josep; Szczubiał, Marek; Piech, Tomasz; Bochniarz, Mariola; Wawron, Władysław; Tvarijonaviciute, Asta

    2015-09-26

    Pyometra is a serious bacterial infection of the uterus affecting female dogs and manifests as an accumulation of pus in the uterine lumen. The aim of the study was to assess changes in serum interleukin (IL)-6 and IL-10 concentrations in bitches with pyometra undergoing ovariohysterectomy. Blood samples were collected from healthy bitches (controls) and bitches with pyometra before surgery, and 3 and 10 days after ovariohysterectomy. Before surgery, bitches with pyometra had significantly higher serum concentrations of IL-6 and IL-10 than the controls. After surgery, the serum concentration of IL-6 and IL-10 decreased significantly. In healthy dogs, the concentration of IL-6 and IL-10 showed a significant increase 3 days after surgery followed by a decrease on day 10. An increase in serum concentrations of IL-6 and IL-10 was present before surgery in bitches with pyometra and 3 days after ovariohysterectomy in healthy controls. Concentrations decreased after ovariohysterectomy and/or proper healing, suggesting that these cytokines can be useful for assessment of the postoperative period in bitches.

  9. Photodynamic therapy affects the expression of IL-6 and IL-10 in vivo

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    Gollnick, Sandra O.; Musser, David A.; Henderson, Barbara W.

    1998-05-01

    Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

  10. B cells produce less IL-10, IL-6 and TNF-α in myasthenia gravis.

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    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Parman, Yeşim G; Direskeneli, Haner; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-06-01

    B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.

  11. Occupational exposure to trichloroethylene and serum concentrations of IL-6, IL-10, and TNF-alpha.

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    Bassig, Bryan A; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Shen, Min; Smith, Martyn T; Qiu, Chuangyi; Ge, Yichen; Ji, Zhiying; Reiss, Boris; Hosgood, H Dean; Liu, Songwang; Bagni, Rachel; Guo, Weihong; Purdue, Mark; Hu, Wei; Yue, Fei; Li, Laiyu; Huang, Hanlin; Rothman, Nathaniel; Lan, Qing

    2013-07-01

    To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross-sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL-6, IL-10, and TNF-α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL-10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL-10 was >60% and statistically significant in workers exposed to <12 ppm as well as in workers with exposures ≥ 12 ppm of TCE, compared to unexposed workers. No significant differences in levels of IL-6 or TNF-α were observed among workers exposed to TCE compared to unexposed controls. Given that IL-10 plays an important role in immunologic processes, including mediating the Th1/Th2 balance, our findings provide additional evidence that TCE is immunotoxic in humans.

  12. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.

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    Stappers, M H T; Thys, Y; Oosting, M; Plantinga, T S; Ioana, M; Reimnitz, P; Mouton, J W; Netea, M G; Joosten, L A B; Gyssens, I C

    2014-12-01

    Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

  13. Differential T Cell Cytokine Receptivity and Not Signal Quality Distinguishes IL-6 and IL-10 Signaling during Th17 Differentiation.

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    Jones, Lindsay L; Alli, Rajshekhar; Li, Bofeng; Geiger, Terrence L

    2016-04-01

    How a large number of cytokines differentially signal through a small number of signal transduction pathways is not well resolved. This is particularly true for IL-6 and IL-10, which act primarily through STAT3 yet induce dissimilar transcriptional programs leading alternatively to pro- and anti-inflammatory effects. Kinetic differences in signaling, sustained to IL-10 and transient to IL-6, are critical to this in macrophages. T cells are also key targets of IL-6 and IL-10, yet how differential signaling in these cells leads to divergent cellular fates is unclear. We show that, unlike for macrophages, signal duration cannot explain the distinct effects of these cytokines in T cells. Rather, naive, activated, activated-rested, and memory CD4(+) T cells differentially express IL-6 and IL-10 receptors in an activation state-dependent manner, and this impacts downstream cytokine effects. We show a dominant role for STAT3 in IL-6-mediated Th17 subset maturation. IL-10 cannot support Th17 differentiation because of insufficient cytokine receptivity rather than signal quality. Enforced expression of IL-10Rα on naive T cells permits an IL-10-generated STAT3 signal equivalent to that of IL-6 and equally capable of promoting Th17 formation. Similarly, naive T cell IL-10Rα expression also allows IL-10 to mimic the effects of IL-6 on both Th1/Th2 skewing and Tfh cell differentiation. Our results demonstrate a key role for the regulation of receptor expression rather than signal quality or duration in differentiating the functional outcomes of IL-6 and IL-10 signaling, and identify distinct signaling properties of these cytokines in T cells compared with myeloid cells.

  14. Expression and significance of TNF-α, IL-6, and IL-10 in the serum in patients with mycoplasma pneumonia

    Institute of Scientific and Technical Information of China (English)

    Dong-Hai Zhang

    2016-01-01

    Objective:To explore the expression and clinical significance of TNF-α, IL-6, and IL-10 in the serum in patients with mycoplasma pneumonia (MPP).Methods:A total of 120 patients with MPP who were admitted in our hospital from August, 2014 to June, 2015 were included in the study and served as the observation group, while 60 healthy children who came for physical examinations were served as the control group. The serum levels of IL-6, IL-10, and TNF-α in the observation group at the acute phase and recovery phase were detected and compared with the control group. The serum levels of IL-6, IL-10, and TNF-α in mild and severe MPP patients were compared. The levels of IL-6, IL-10, and TNF-α in the serum and pleural fluid in MPP patients with or with no fibrosis change were compared and analyzed. Results:When compared with the control group, the serum TNF-α and IL-6 levels in the observation group at the acute phase and recovery phase were significantly elevated, while IL-10 level was significantly reduced. The serum TNF-α and IL-6 levels in MPP patients at the acute phase were significantly lower than those at the recovery phase, while IL-10 level was significantly higher than that at the recovery phase. The serum TNF-α and IL-6 levels in the severe group were significantly higher than those in the mild group, while IL-10 level was significantly lower than that in the mild group. TNF-α level in the pleural fluid in MPP patients with fibrosis change was significantly higher than that in MPP patients with no fibrosis change, while the comparison of IL-6 and IL-10 was not statistically significant. TNF-α level in MPP patients with fibrosis change in the pleural fluid was significantly higher than that in the serum, while the comparison of IL-6 and IL-10 was not statistically significant. IL-6, IL-10, and TNF-α levels in MPP patients with no fibrosis change in the pleural fluid were not statistically different from those in the serum.Conclusions:TNF-α, IL-6, and

  15. Effect of acupuncture on TNF-alpha, IL-1b and IL-10 concentrations in the peritoneal exudates of carrageenan-induced peritonitis in rats Efeito da acupuntura sobre a concentração de TNF-alfa, IL-1b e IL-10 no exsudato peritoneal de ratos com peritonite induzida por carragenina

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    Márcia Valéria Rizzo Scognamillo-Szabó

    2005-02-01

    Full Text Available Acupuncture is an ancient and empirical therapeutic procedure known by its efficacy in the treatment of pain. However, the influence of acupuncture on inflammatory process is still poorly understood and additional research is needed. In this work, we investigated the mechanism of action of manual acupuncture on the inhibition of neutrophil migration to the peritoneal cavity induced by the inflammatory stimulus carrageenan in Wistar rats. Previous results from our laboratory showed that this anti-inflammatory effect is not due to endogenous corticoid release. Furthermore, the concentration of IL-1b, but not of TNF-alpha or IL-10 in the carrageenan-induced exudates was reduced in the acupuncture group. Further research will be needed to elucidate the mechanisms involved in the anti-inflammatory action of acupuncture as described here.A acupuntura é método terapêutico milenar reconhecido por sua eficácia no tratamento da dor, porém seu efeito sobre processos inflamatórios é ainda pouco conhecido e maiores estudos são necessários. Neste trabalho, é investigado o mecanismo de ação da acupuntura manual sobre a inibição na migração de neutrófilos para a cavidade peritoneal induzida por carragenina em ratos Wistar. Resultados prévios indicam que esse efeito antiinflamatório não depende de hormônios corticóides. Entretanto, as concentrações de IL-1b no exsudato induzido por carragenina foram reduzidas pelo tratamento com acupuntura. Por outro lado os níveis de TNF-alfa e IL-10 não foram afetados pelo tratamento. Mais pesquisas poderão elucidar os mecanismos envolvidos na ação antiinflamatória da acupuntura.

  16. Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in Weil's syndrome.

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    Kyriakidis, Ioannis; Samara, Pinelopi; Papa, Anna

    2011-05-01

    Studies on cytokine levels in Weil's syndrome are lacking. In this study, TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels were measured in 44 serum samples of patients diagnosed with Leptospira interrogans serovar icterohaemorrhagiae infection. TNF-α levels linked with pulmonary hemorrhagic implications, while elevated sTNFR1 and IL-10 levels linked with fatal cases. IL-6 and IL-8 did not seem to affect the outcome of the disease. Immune response pattern in Weil's syndrome bears resemblance to other patterns described for hemorrhagic fevers. IL-10/TNF-α ratio is proposed as a marker for prognosis.

  17. 急性心肌梗死血清IL-6IL-10水平的变化

    Institute of Scientific and Technical Information of China (English)

    李永东; 刘丹

    2008-01-01

    目的:探讨IL-6IL-10对急性心肌梗死(AMI)的影响.方法:选择AMI患者30例和对照组30例.AMI组于发病后24 h、2周检测血清IL-6IL-10.结果:(1)AMI组血清IL-6IL-10水平及IL-6/IL-10比值高于对照组,差异有显著性;(2)相关分析:①AMI与IL-6IL-10呈正相关;②IL-6IL-10、WBC呈正相关.结论:AMI后血清IL-6IL-10水平增高,其变化参与AMI的发生和发展.

  18. The early IL-6 and IL-10 response in trauma is correlated with injury severity and mortality

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    Stensballe, J; Christiansen, M; Tønnesen, E;

    2009-01-01

    in the first 24 h after trauma and to assess the relationship with severity of injury and mortality. METHODS: Prospective, descriptive cohort study in a Level 1 trauma centre, Copenhagen, Denmark. We included 265 consecutive adult trauma patients admitted directly from the accident scene during an 18-month...... period. Serum levels of IL-6 and IL-10 were measured upon arrival and at 6, 12, and 24 h after admittance using an enzyme-linked immunosorbent assay. Correlation analysis was used to assess the relationship between Injury Severity Score (ISS) and levels of IL-6 and IL-10. Analysis of variance was used...

  19. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans

    DEFF Research Database (Denmark)

    Steensberg, Adam; Fischer, Christian Philip; Keller, Charlotte

    2003-01-01

    The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion...... number without effects on plasma epinephrine, body temperature, mean arterial pressure, or heart rate. In conclusion, this study demonstrates that physiological concentrations of IL-6 induce an anti-inflammatory rather than an inflammatory response in humans and that IL-6, independently of TNF......-induced leukocyte trafficking....

  20. Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation

    NARCIS (Netherlands)

    Dokter, Willem; Koopmans, S.B.; Vellenga, E

    1996-01-01

    Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate

  1. Study on Cytokines IL-2, IL-6, IL-10 in Patients of Chronic Allergic Rhinitis Treated with Acupuncture

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objectives: To observe the plasmatic concentration of IL-6, IL-10 and IL-2 in the patient of chronic allergic rhinitis before and after acupuncture therapy. Methods: Cytokine levels were determined before and after treatment in 30 healthy volunteers (Group A) and 90 patients of chronic allergic rhinitis (Group B) with an increased plasma IL-10 level. Group B was then divided into 3 subgroups: 30 patients treated with real acupuncture (Group B1); 30 patients treated with sham acupuncture (Group B2); 30 non-treated patients (Group B3). Results: The allergic subjects of group B1, compared with controls, showed a significant reduction of IL-10 after a specific treatment with acupuncture (P<0.05). On the other hand, in those patients treated with sham acupuncture (B2) as well as in non-treated patients (B3), the IL-10 values remained high and unchanged. There was a statistically significant change in IL-2 values at 24 hours (P<0.05) after real acupuncture (Groups A, B1), however the values remained within normal ranges. The IL-6 do not change after therapy. Conclusion: The acupuncture treatment can reduce plasmatic level of IL-10 in chronic allergic rhinitis.

  2. Interactions between diet, lifestyle and IL10, IL1B, and PTGS2/COX-2 gene polymorphisms in relation to risk of colorectal cancer in a prospective Danish case-cohort study.

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    Vibeke Andersen

    Full Text Available BACKGROUND & AIMS: Diet contributes to colorectal cancer development and may be potentially modified. We wanted to identify the biological mechanisms underlying colorectal carcinogenesis by assessment of diet-gene interactions. METHODS: The polymorphisms IL10 C-592A (rs1800872, C-rs3024505-T, IL1b C-3737T (rs4848306, G-1464C (rs1143623, T-31C (rs1143627 and PTGS2 (encoding COX-2 A-1195G (rs689466, G-765C (rs20417, and T8473C (rs5275 were assessed in relation to risk of colorectal cancer (CRC and interaction with diet (red meat, fish, fibre, cereals, fruit and vegetables and lifestyle (non-steroid-anti-inflammatory drug use and smoking status was assessed in a nested case-cohort study of nine hundred and seventy CRC cases and 1789 randomly selected participants from a prospective study of 57,053 persons. RESULTS: IL1b C-3737T, G-1464C and PTGS2 T8473C variant genotypes were associated with risk of CRC compared to the homozygous wildtype genotype (IRR=0.81, 95%CI: 0.68-0.97, p=0.02, and IRR=1.22, 95%CI: 1.04-1.44, p=0.02, IRR=0.75, 95%CI: 0.57-0.99, p=0.04, respectively. Interactions were found between diet and IL10 rs3024505 (P-value for interaction (P(int; meat=0.04, fish=0.007, fibre=0.0008, vegetables=0.0005, C-592A (P(int; fibre=0.025, IL1b C-3737T (Pint; vegetables=0.030, NSAID use=0.040 and PTGS2 genotypes G-765C (P(int; meat=0.006, fibre=0.0003, fruit 0.004, and T8473C (P(int; meat 0.049, fruit=0.03 and A-1195G (P(int; meat 0.038, fibre 0.040, fruit=0.059, vegetables=0.025, and current smoking=0.046. CONCLUSIONS: Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene-environment interactions may identify genes and environmental factors involved in colorectal carcinogenesis.

  3. Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL-6, IL-10, pstat3, and SOCS3.

    Science.gov (United States)

    van de Vyver, M; Engelbrecht, L; Smith, C; Myburgh, K H

    2016-06-01

    High-intensity exercise results in immune activation. This study determined whether (a) there is concordance between serum MPO and neutrophil and/or monocyte intracellular MPO content; (b) peripheral blood mononuclear cells respond to inflammatory interleukins (ILs) by increasing intracellular signaling. Healthy male (n = 12) volunteers participated in high-intensity running (12 × 5 min, 10% decline, 15 km/h). Blood sample (pre, post, 4 h) analyses included serum concentrations of IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, matrix metalloprotease-9 (MMP-9) and creatine kinase (CK). Intracellular IL-6, IL-10, MPO and STAT3/SOCS3 signaling were assessed in mononuclear cells. CK (1573 ± 756 u/L), MMP-9 (101 ± 27 ng/mL), neutrophil (9.89 ± 0.76 × 10(9) cells/L) and monocyte counts (1 ± 0.08 × 10(9) cells/L) increased at 4 h. At 4 h serum (7.1 ± 1.3 ng/mL) and monocyte MPO (1.7-fold) increased, whereas neutrophil MPO decreased (0.8-fold). Intracellular monocyte IL-10 and IL-6 decreased by 15% and 20-30%, respectively, coinciding with elevations in serum IL-10 of 14.5 ± 4.7 pg/mL and IL-6 of 5.4 ± 2.9 pg/mL, suggesting immune cell cytokine release in response to exercise. Intracellular PBMC p-STAT3 to total STAT3 ratio increased from pre to 4 h. Circulating monocytes are responsive to increased serum IL-6 suggesting a negative feedback loop via STAT3 signaling. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. The effect of valtrex on T cell subset and IL2, IL6 and IL10 level in patients with herpes zoster

    Institute of Scientific and Technical Information of China (English)

    Gui-E Wang; Jian Chen; Ling Chen

    2015-01-01

    Objective:To explore the effects of valtrex on T cell subset and IL2, IL6 and IL10 level in patients with herpes zoster.Methods: 120 patients with herpes zoster in our hospital were analyzed. The serum T cell subset and IL2, IL6 and IL10 were detected by Western Blotting. Healthy volunteers were enrolled as control group.Results: The CD4+ level was increased significantly while the CD8+ decreased significantly, and the ratio of the two increased too (P all<0.01). The IL6 and IL10 levels were increased significantly (P<0.01). But no significant change in IL2 level was observed.Conclusion:Valtrex is effective on herpes zoster by regulating T cell subset, IL6 and IL10 levels.

  5. IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants

    Directory of Open Access Journals (Sweden)

    Yanamandra Krishna

    2006-04-01

    Full Text Available Abstract Background Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection. Methods Infectious complications were retrospectively determined in 293 (233 African-American (AA, 57 Caucasian and 3 Hispanic mechanically ventilated very low birth weight (VLBW infants ( Results The IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69% compared to 94/204 (46% in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021. The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35% of 40 infants with the GG genotype, 71 (49% of 145 infants with the GA genotype and 63 (58% of 108 infants with the AA genotype (p = 0.036. Infants with the A allele (AA or GA genotypes had an incidence of late BSI that was 134/253 (53% compared to 14/40 (35% in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035. The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022. This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003. Conclusion The IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.

  6. The changes of frequencies of regulatory T cells in peripheral blood and serum levels of IL-1β ,IL-6 and IL-10 in patients with HBV-related liver cirrhosis%乙型肝炎肝硬化患者外周血调节性T细胞频率及血清IL-1β、IL-6IL-10水平的变化

    Institute of Scientific and Technical Information of China (English)

    李晨; 邢少军; 段学章; 胡瑾华; 柳芳芳; 王慧芬; 万谟彬

    2012-01-01

    目的 检测未抗病毒治疗的乙型肝炎肝硬化患者外周血调节性T细胞(Treg细胞)及其亚群频率和血清IL.1 β、IL-6IL-10水平,以探讨乙型肝炎肝硬化患者免疫功能的变化.方法 在20例健康对照人群、17例慢性乙型肝炎(CHB)患者和38例乙型肝炎肝硬化(LC)患者,采用流式细胞仪检测外周血CD4+CD25+Foxp3+(Treg)细胞频率、CD4+CD39+Foxp3+(CD39+Freg)细胞和CD4+CTLA-4+Foxp3+(CTLA-4+Freg)细胞频率;采用ELISA法检测血清IL-1β、IL-6IL-10水平.结果 LC患者Treg细胞频率、CD39+Treg细胞频率、CTLA-4+Treg细胞频率、血清IL-1β、IL-6IL-10水平均高于正常人(P均<0.01)和CHB患者(P<0.05或P<0.01);失代偿期LC患者Treg细胞频率、CD39+Treg细胞频率、IL-6水平高于代偿期患者(P均<0.01);LC患者Treg细胞频率与CD39+Treg细胞频率(r=0.474,P<0.01)、CTLA-4+Treg细胞频率均呈正相关(r=0.330,P<0.05),Treg细胞频率(r=0.381,P<0.05)、CD39+Treg细胞频率(r=0.333,P<0.05)与TBil呈正相关.Treg细胞频率(r=-0.549,P<0.01)、CD39+Treg细胞频率(r=-0.437,P<0.01)、CTLA-4+Treg细胞频率(r=-0.368,P<0.01)与PTA呈负相关,CD39+Treg细胞频率与AST呈正相关(r=0.406,P<0.05).结论 Treg细胞及其亚群频率和IL-1β、IL-6IL-10水平的变化可作为临床初始治疗的乙型肝炎肝硬化患者辅助检查指标之一.%Objective To investigate the frequencies of regulatory T cells (Treg cells), its subgroups and serum levels of IL-1 B ,IL-6 and IL-10 in HBV-related liver cirrhosis. Methods In 20 healthy persons, 17 patients with chronic hepatitis B (CHB) and 38 with HBV-related liver cirrhosis (LC),the frequencies of CD4+ CD25+Fox3+ cells (Treg cells ),CD4+CD39+Fox3+cells(CD394Treg cells),and CD4+CTLA-4+ Fox3+cells(CTLA-4+ Treg cells) were detected by flow cytometry. The serum levels of IL-1 B , IL-6 and IL-10 were detected by ELISA. Results The frequencies of Treg cells,CD39+ Treg cells and CTLA-4Treg cells and the serum levels of IL

  7. Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

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    Xuelian Yu

    Full Text Available BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1 are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1 patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1 and non-flu influenza like illness (non-ILIs cases with mild symptoms (mild patients, P(H1N1 vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1 and non-ILIs patients with severe symptoms (severe patients. Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1 patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1 patients. Higher IL-10 secretion in P(H1N1 vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1 infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1 patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1 patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression, but the underlying mechanism awaits

  8. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma.

    Science.gov (United States)

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  9. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma

    Science.gov (United States)

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  10. Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease

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    Alvarez Victoria

    2009-08-01

    Full Text Available Abstract Background Chronic inflammation is a characteristic of Alzheimer's disease (AD. An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6, and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10. Methods We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. Results We replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01, controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4 genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03 and North Spain (SF = 2.0, p = 0.09. Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. Conclusion We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.

  11. Effect of remifentanil on serum IL-6, IL-8, and IL-10 in patients undergoing laparoscope cholecystectomy%雷米芬太尼对腹腔镜胆囊切除术患者IL-6、IL-8和IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    尹罗庚; 袁玉萍; 周红云; 庄建伟; 吴文玉; 丁德威

    2006-01-01

    目的 观察全麻下雷米芬太尼与芬太尼对腹腔镜胆囊切除术(LC)患者白细胞介素(IL)-6、IL-8和IL-10的影响.方法 20例LC患者,随机分为两组,每组10例.雷米芬太尼组(Ⅰ组)和芬太尼组(Ⅱ组),分别测定麻醉诱导前、气腹手术前、气腹手术后0.5 h、术毕0.5 h、术后24 h的血清IL-6、IL-8和IL-10的水平.结果 IL-6、IL-8和IL-10在创伤后1~1.5 h开始升高,IL-6的变化最早,IL-8、IL-10在手术结束时逐渐升高,IL-6、IL-8在术后24 h仍在继续上升(P<0.05),而IL-10则有不升或缓升趋势.IL-10IL-6和IL-8的升高有一定的平衡作用.组间比较,术后24 hⅠ组IL-6、IL-8较Ⅱ组都有明显升高(P<0.01).结论 与芬太尼相比,雷米芬太尼可更为有效地减轻创伤刺激后IL-6、IL-8和IL-10的释放.

  12. Change and Clinical Significance of Serum IL-6, IL-10, and IL-17 level in Children with Hand, Foot, and Mouth Disease%手足口病患儿血清IL-6IL-10、IL-17水平的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    黄小霏; 檀卫平; 江润昌

    2012-01-01

    [Objective] To study the changes and clinical significance of serum interleukin (IL)-6, IL-10, and IL-17 levels in the children with hand foot and mouth disease (HFMD). [Method] The serum concentration of IL-6, IL-10, and IL-17 in 19 cases of HFMD children ( acute stage and convalescence ) and 20 cases of healthy controls were measured by ELJSA. The cytokines levels were compared. [Results] 1.Compared with healthy controls, the levels of IL-6, IL-10, and IL-17 in acute stage of HFMD were significantly increased in HFMD children (P 0.05 ), However the levels of IL-10 in convalescence of HFMD were higher than healthy children (P 0.05). [Conclusions] l.The levels of IL-6 and IL-17 were significantly increased in acute stage of HFMD children. 2. The persistent elevation of serum IL-10 level was found in HFMD patients after convalescence.%[目的]探讨手足口病(HFMD)患儿外周血白介素-6(IL-6)、白介素-10(IL-10)、白介素-17(IL-17)水平及其在HFMD发展过程中的变化.[方法]本实验采用酶联免疫吸附实验(ELISA)双抗体夹心法测定19例HFMD患儿(急性期、恢复期)及同期20例健康体检儿童血清IL-6IL-10、IL-17的含量;并对HFMD患儿急性期、恢复期及健康儿童进行两两比较,了解IL-6IL-10、IL-17在HFMD发展过程中的变化.[结果]1、手足口病患儿急性期IL-6IL-10及IL-17水平显著高于健康对照组(P< 0.01);恢复期IL-6及IL-17水平与对照组比较无显著差异(P>0.05).而IL-10水平仍高于健康对照组(P<0.01).2、急性期IL-6IL-10呈负相关关系(P< 0.05);IL-6与IL-17呈正相关关系(P< 0.01);IL-10与IL-17呈负相关关系(P<0.05).恢复期:IL-6IL-10呈负相关关系(P< 0.05);IL-6与IL-17呈正相关关系(P<0.01);IL-10与IL-17无相关关系(P>0.05).[结论]手足口病患儿急性期炎症细胞因子( IL-6、IL-17)水平显著升高,而抑制性细胞因子IL-10水平升高持续到恢复期.

  13. 手足口病患儿血清IL-6IL-10、IL-17水平的变化及其临床意义%The change and clinical significance of serum IL-6IL-10 and IL-17 level in children with hand,foot and mouth disease

    Institute of Scientific and Technical Information of China (English)

    黄小霏; 范联; 陈国华

    2012-01-01

    目的 探讨手足口病(HFMD)患儿外周血白介素(IL)-6IL-10、IL-17水平及其在HFMD发展过程中的变化.方法 采用酶联免疫吸附实验(ELISA)双抗体夹心法测定56例HFMD患儿(急性期、恢复期)及同期40例健康对照组儿童血清IL-6IL-10、IL-17的含量;并对HFMD患儿急性期、恢复期及健康对照组进行两两比较;HFMD患儿中重症患儿、普通患儿及健康对照组进行两两比较,了解IL-6IL-10、IL-17在HFMD发展过程中的变化.结果 (1)HFMD患儿急性期IL-6IL-10及IL-17水平显著高于健康对照组(P0.05).而IL-10水平仍高于健康对照组(P0.05).结论 HFMD患儿急性期炎性细胞因子(IL-6、IL-17)水平显著升高,而抑制性细胞因子IL-10水平升高持续到恢复期.%Objective To study the changes and clinical significance of serum interleukin(IL)-6 , IL-10, IL-17 levels in the children with hand foot and mouth disease(HFMD). Methods The serum concentration of IL-6 ,IL-10,I1-17 in 56 cases of HFMD chil-dren(acute stage and recovery stage) and 40 cases of healthy controls were measured by ELISA. The cytokines levels were compared pairly. Results (l)Compared with healthy controls,The levels of IL-6,IL-10 and IL-17 in acute stage of HFMD were significantly increased in HFMD children(P0. 05) , However the levels of IL-10 in recovery stage of HFMD were higher than healthy children(P0. 05). Conclusion The levels of IL-6 and IL-17 were significantly increased in acute stage of HFMD children. The persistent elevation of serum IL-10 level was found in HFMD patients after convalescence.

  14. IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study

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    Victor Mardini

    2016-03-01

    Full Text Available Introduction Prenatal cocaine exposure (PCE is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10 both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. Methods In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN and 99 non-exposed newborns (NEN were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. Results After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]. Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM. Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM, with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures. Conclusions IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

  15. 脑胶质瘤患者血清IL-6、IL-8、IL-10和TNF-α的表达及临床意义%The Expression of IL-6, IL-8, IL-10 and TNF-α in Serum of Glioma and Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    李春生; 张朋军

    2013-01-01

    [Purpose] To explore the diagnostic value of serum interleukin-6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF-α) for glioma. [Materials and methods] The content of IL-6, IL-8, IL-10 and TNF-α in the healthy control group, the low-grade gliomas group and the high-grade gliomas group were detected by Luminex 200. [Results] Compared to the healthy control group, IL-6, IL-8, and TNF-α in the low-grade gliomas group showed significantly different, IL-6, IL-8, IL-10 and TNF-α in the high-level group of glioma showed significantly different. Compared to the low-grade gliomas Group, IL-6, IL-10 and TNF-α in the high-grade gliomas showed significantly different. When we discriminated the low-grade gliomas and high-grade gliomas, the best indicators was IL-10, and the diagnostic sensitivity and specificity were 74.90% and 65.80%, respectively. When the IL-6, IL-10 and TNF-α were combined, the sensitivity and specificity were 92.30% and 93.10%, respectively. [Conclusion] IL-6, IL-10 and TNF-α joint diagnostic value showed significant improvedment when compared to the individual indicators. It may provide a auxiliary method for brain the clinical diagnosis of glioma.%  [目的]探讨血清中白介素6(IL-6)、IL-8、IL-10和肿瘤坏死因子(TNF-α)对于脑胶质瘤的诊断价值。[材料与方法]分别检测健康对照组、低级别脑胶质瘤组和高级别脑胶质瘤组中IL-6、IL-8、IL-10和TNF-α的含量。[结果]与健康对照组比较,低级别脑胶质瘤组的IL-6、IL-8和TNF-α有统计学差异,高级别脑胶质瘤组的IL-6、IL-8、IL-10和TNF-α均具有统计学差异。与低级别脑胶质瘤组相比较,高级别脑胶质瘤组的IL-6IL-10和TNF-α有统计学差异。其中区分低级别脑胶质瘤和高级别脑胶质瘤的诊断价值最好的指标为IL-10,其诊断灵敏性和特异性分别为74.90%和65.80%。IL-6IL-10和TNF-α联合检测时其灵敏性和特异性分别为92.30%和93.10%。[结论]证实IL

  16. Clinical significance of detecting serum levels of TNF-α, IL-10, IL-8 and IL-6 in patients with Breast cancer%乳腺癌患者血清IL-6、IL-8、IL-10和TNF-α的水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    王治伟; 迟琼; 万利

    2012-01-01

    目的 探讨乳腺癌患者血清中IL--6、IL-8、IL-10和TNF-α水平与乳腺癌发病的关系.方法 应用放射免疫分析方法检测50例乳腺癌患者不同时期血清IL-6、IL-8、IL-10和TNF-α水平,并与30例正常者对照比较.结果 乳腺癌患者活动期血清中IL-6、IL-8和TNF-α的含量显著高于缓解期和对照组,IL-10含量显著低于缓解期和对照组.缓解期IL-6、IL-8、IL-10和TNF-α含量与对照组比较差异无统计学意义(P>0.05).活动期IL-6、IL-8表达水平与TNF-α呈正相关,与IL-10呈负相关.结论 乳腺癌患者活动期IL-10表达水平降低,IL-6、IL-8和TNF-α 表达水平升高,使体内免疫调节失衡,从而成为乳腺癌患者病因之一.乳腺癌患者血清中IL-6、IL-8、IL-10和TNF-α水平与疾病严重程度显著相关.

  17. Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection.

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    Rúbia M de Medeiros

    Full Text Available Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs and rapid (RPs progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93-136.5 months for SPs and 7.5-16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals-subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months-and those receiving HAART. The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals.

  18. Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection

    Science.gov (United States)

    de Medeiros, Rúbia M.; Valverde-Villegas, Jacqueline M.; Junqueira, Dennis M.; Gräf, Tiago; Lindenau, Juliana D.; de Mello, Marineide G.; Vianna, Priscila; Almeida, Sabrina E. M.; Chies, Jose Artur B.

    2016-01-01

    Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals. PMID:27214135

  19. 肝硬化患者血清AFP、TNF-α、IL-6IL-10检测的临床意义%Clinical Significance of Combined Detection of Changes of Serum AFP, TNF-α, IL-6, IL-10 Levels in Patients with Liver Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    张家明; 王文; 姚孝明; 施建丰

    2007-01-01

    目的:探讨了肝硬化患者血清中AFP、TNF-α、IL-6IL-10水平及意义.方法:分别应用RIA和ELISA对63例肝硬化患者进行了血清AFP、TNF-α、IL-6IL-10水平测定,并与35例正常健康人做比较.结果:肝硬化患者血清AFP、TNF-α、IL-6IL-10水平均非常显著的高于正常人组(P<0.01),且AFP水平与TNF-α、IL-6IL-10水平呈明显的正相关(r=0.5988、0.6138、0.6284,P<0.01).结论:AFP、TNF-α、IL-6IL-10在肝硬化的防病机理中有一定的临床价值.

  20. 丙型肝炎患者血清TNF,IL-6,IL-10及其临床意义%Clinical Significance of Changes of Serum Tumor Necrosis Factor (TNF)and Interleukin -6(IL-6), Interleukin -10(IL-10) Levels in Patients with Hepatitis C

    Institute of Scientific and Technical Information of China (English)

    郑洁; 李红; 王玉平; 高勇

    2004-01-01

    目的:探讨了丙型肝炎患者血清中TNF、IL-6IL-10水平及意义.方法:分别应用ELISA法和放免法检测了58例丙型肝炎患者血清中TNF、IL-6IL-10水平,并与35名正常健康人作比较.结果:丙型肝炎患者血清中TNF、IL-6IL-10水平均非常显著地高于正常人水平(P<0.01),肝硬化组为甚,且TNF与IL-6IL-10呈正相关(r=0.6135, 0.6225, P<0.01).结论:TNF、IL-6IL-10在丙型肝炎病毒感染的致病机理中有一定的临床价值.

  1. The expression of serum IL-6, IL-10, IL-12 level in gastrointestinal neoplasm and its significance%血清IL-6IL-10、IL-12在消化道肿瘤中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    姚琪远; 张群华; 倪泉兴; 张延龄

    2000-01-01

    目的探讨消化道肿瘤患者血清IL-6IL-10、IL-12的变化及其意义.方法应用酶联免疫法测定了胃癌、结肠癌及健康者血清IL-6IL-10、IL-12含量,比较其相互间的关系.结果胃癌和结肠癌组IL-10、IL-12含量低于对照组;IL-6含量则高于对照组,且随着肿瘤临床病理分期的进展而不断升高;胃癌血清IL-6IL-10、IL-12含量与结肠癌接近.结论消化道肿瘤患者血清细胞因子IL-6IL-10、IL-12的变化可能与肿瘤的生长及机体抗肿瘤免疫功能的受损有关.

  2. Evaluation of TNF-α, IL-10 and IL-6 Cytokine Production and Their Correlation with Genotype Variants amongst Tuberculosis Patients and Their Household Contacts.

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    Lavanya Joshi

    Full Text Available Household contacts of diagnostically established tuberculosis (TB patients are highly susceptible to disease development. It is surmised that cytokines perhaps play a synergistic and a prognostic role in the activation of the otherwise latent infection in these house hold contacts. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating the immune regulation and the progression of the disease. The cytokines thus released in a paracrine manner in serum may also provide an indirect measure of the cytokine function.The present study was aimed to evaluate the levels of TNF-α, IL-10 & IL-6 cytokines and their correlation with genotype variants amongst tuberculosis patients and their household contacts.The cytokine levels were estimated in serum by enzyme-linked immunosorbent assay (ELISA and their polymorphisms were studied by amplification refractory mutation system polymerase chain reaction (ARMs PCR in active pulmonary tuberculosis patients (APTB = 150, household contacts (HHC = 190, and healthy controls (HC = 150.The median values of TNF-α cytokine were significantly high among APTB and HHC compared to HCs (P< 0.0001 and 0.0001. IL-6 levels also were elevated among APTB compared to HHC and HC, and a significant difference was observed between APTB and HHC at P<0.0001; APTB & HC at P< 0.04; HHC & HC at P< 0.01. The IL-10 levels were low in APTB compared to HHC and HCs and no significant difference was observed. TNF-α/IL-10 ratio was significant and indicated Th1 predominance in APTB and HHC. IL-6/IL-10 showed pronounced Th1 expression in APTB and Th2 in HHC and HC. The ROC analysis indicated that both IL-10 and IL-6 can be used to decide the risk of exposed individual to a disease. The results of multivariate analysis indicate that IL-10 (-1082 GA genotype was significantly associated with p<0.028 in APTB. No significant association was observed between genotypes, other serum

  3. The Effect of Montelukast on the Levels of IL-6,IL-8 and IL-10 in Patients with Bronchial Asthma%孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

    Institute of Scientific and Technical Information of China (English)

    许成

    2012-01-01

    Objective To explore the effect of Montelukaat on serum IL-6,IL-8 and IL-10 levels in patients with bronchial asthma. Methods Serum TL-6,TLS (with RIA) ,IL-10 (with ELISA) levels were measured in 31 patients after Montelukast treatment with bronchial asthma as well as in 35 normal healthy controls. Result Before treatment serum IL-6, IL-8 levels in the asthma group were significantly higher than those in controls (P<0.01). While the IL-10 level was undoubtedly lower than that in the controls (P <0.01). After treatment, the serum IL-6, IL-8 and IL-10 levels were still significantly (P<0.05). Conclusion Montelukast treatment could bring about some regulatory effect on serum IL-6, IL-8 and IL-10 levels in patients with asthma and furthermore reducing the severity of inflammation and enhancing remission.%目的 探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响.方法 应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较.结果 支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05).结论 孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转.

  4. Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome.

    Science.gov (United States)

    Kyriakidis, Ioannis; Papa, Anna

    2013-07-01

    It is generally accepted that the pathogenesis of hantavirus infections is the result of virus-mediated host immune response. Hantaviruses, and mainly Dobrava-Belgrade virus, are present in Greece, and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.

  5. 热化疗治疗非小细胞肺癌对IL-2、IL-6、IL-8、IL-10及TNF的影响%Effect of thermochemotherapy on levels of IL-2 ,IL-6 ,IL-8 ,IL-10 and TNF in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李新民; 尉继伟; 刘治邦; 刘建国

    2014-01-01

    目的 探讨热化疗治疗非小细胞肺癌(NSCLC)对白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)及肿瘤坏死因子(TNF)的影响.方法 回顾性分析大同大学附属医院2004年10月至2013年1月收治的134例NSCLC患者,进行热疗联合NP方案化疗(NVB+ DDP),并分别在治疗前、治疗3个周期后、治疗6个周期后、治疗结束后3个月对患者血清中IL-2、IL-6、IL-8、IL-10及TNF的变化进行监测.结果 热化疗3个周期后,IL-2、TNF水平逐渐增高,明显高于治疗前;IL-6、IL-8和IL-10水平明显低于化疗前.热化疗6个周期后,血IL-6、IL-8、IL-10、IL-2和TNF都有所下降,其中IL-2、TNF浓度显著低于化疗3个周期后的水平.热化疗结束后3个月,血IL-6、IL-8、IL-10水平继续下降;而IL-2、TNF浓度逐渐增高,低于化疗3个周期后的水平,但高于治疗前水平.结论 热化疗治疗NSCLC对IL-2、TNF水平有明显的增高作用,而对IL-6、IL-8、IL-10有降低作用.%Objective To investigate the effect of hot therapy on interleukin-2 (IL-2),interleukin-6 (IL-6),interlerukin-8 (IL-8),interleukin-10 (IL-10) and tumor necrosis factor (TNF) in nonsmall cell lung cancer(NSCLC).Methods One hundred and thirty-four patients with NSCLC,admitted to our hospital from October 2004 to January 2013,received hot therapy and vinorelbine plus cisplatin (NP) chemotherapy.The IL-6,IL-8,IL-10 and TNF level before therapy,after 3 cycles,after 6 cycles and 3 months after chemotherapy were observed.Results IL-2 and TNF levels increased gradually after 3 cycles of hot therapy,and were significant higher than those before therapy.Compared to before therapy,IL-6,IL-8 and IL-10 levels significantly decreased.IL-6,IL-8,IL-10,IL-2 and TNF levels all decreased at 6 months after hot therapy.IL-2 and TNF levels were significant lowered than those of 3 cycles after chemotherapy.IL-6,IL-8 and IL-10 continued to decrease 3 months after the end of

  6. Correlation of IL-6 and IL-10 production following bone marrow transplantation with donor cytokine gene polymorphisms Correlação da produção de IL-6 e IL-10 seguindo o transplante de medula óssea com os polimorfismos de genes de citocinas do doador

    Directory of Open Access Journals (Sweden)

    Jeane E. L. Visentainer

    2008-12-01

    Full Text Available Several candidate gene studies have demonstrated that genetic polymorphisms in cytokine genes contribute to variations in the levels of cytokines produced and this variation may influence the occurrence and severity of complications after stem cell transplantation (HSCT. In this work we compared the serum concentrations of TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 in 13 recipients following HSCT with the TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592, and TGFB1+869,+915 polymorphisms. Serum cytokine levels were assessed using commercial ELISA kits for TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 (BioSource®, Nivelles, Belgium, Europe. Donor/recipient genotypes for these cytokine polymorphisms were analyzed by polymerase chain reaction-sequence-specific primer (PCR-SSP with the Cytokine Genotyping Primers Kit (One Lambda , Canoga Park, CA, USA. We found correlation between the levels of IL-6 and IL-10 concentrations following HSCT and the IL6-174 and IL10-1082,-819,-592 polymorphisms, but not for other cytokines investigated in this study. Those with genotypes associated with low production of IL-6 and IL-10 produced lower levels of these cytokines than those with genotypes associated with high or intermediate production of these cytokines (P Estudos de vários genes candidatos têm demonstrado que polimorfismos genéticos em genes de citocinas contribuem com variações nos níveis de citocinas produzidas e esta variação pode influenciar a ocorrência e gravidade de complicações após o transplante de células-tronco hematopoéticas (TCTH. Neste trabalho comparamos as concentrações séricas de TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 em 13 receptores seguindo o TCTH com os polimorfismos TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592 e TGFB1+869,+915. Os níveis séricos de citocinas foram medidos usando-se kits comerciais de ELISA para TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 (BioSource®, Nivelles, Belgium, Europe. Os genótipos de doadores

  7. The Profile of the Serum Levels of Inflammatory Cytokines TNF-a,IL-6, IL-10 and Captopril Intervention in Reno-hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Li Zhongchen; Liu Fengying

    2005-01-01

    Objectives To observe the profile of the serum levels of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor (TNF-o) and interleukin-10 (IL-10) and evaluate the effects of angiotensin- converting enzyme inhibitor-Captopril on them in renohypertensive rats. Methods Using reformed two-kidney-one-clip (2K 1C ) method, renal hypertensive rats (RHR) were obtained by ligating abdominal aorta.30 Wistar rats were randomized into three groups:sham-operation group (A)、 model control group ( B ) and captopril group (C). All rats were killed after being given the trial drugs 5 weeks, ELISA assays were used to detect the levels of IL-6 and IL-10, the levels of TNF-alpha were measured with radioimmtmoassays.hypertrophy was aggravated in group B significantly,the ratio of left ventricle and body weight(LV/BW) was 0.00318 ±0.00030 (B)and 0.00256 ±0.00040 (A)respectively(P < 0.001 ), the levels of IL-6 and TNF-o increased significantly (P < 0.001 and P < 0.002respectively), whereas the levels of IL-10 were not compared with group B, the LV/BW was 0.00266 ±0.00018 (C) and 0.00318±0.00030 (B) respectively(P < 0.001), the levels of IL-6 and TNF-α decreased significantly ( P < 0.01), whereas the levels of IL-10were not changed between the two groups (P > 0.05);Conclusions Angiotensin converting enzyme inhibitor-captopril can lower the serum levels of proinflammatory cytokines IL-6 and TNF-α effectively,but can not increase the levels of anti-inflammatory cytokine IL-10, it suggests that captopril may have a feature to prevent or slow the development of hypertensive complications by means of lowering the levels of pro-inflammatory cytokines but not by increasing anti-inflammatory cytokine IL-10.

  8. Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and IL-10 secretion from intestinal epithelial cells (IPEC-1).

    Science.gov (United States)

    Parthasarathy, G; Mansfield, L S

    2005-08-10

    Immune responses to gastrointestinal helminth infections have received increasing attention due to similarities to allergen-induced responses. In fact, the whipworm parasite of swine, Trichuris suis, has been used in beginning clinical trials as an antidote to inflammatory bowel disease. This strategy was based on this similarity and the recognition that other worms have been documented to induce anti-inflammatory responses in the host. In an effort to understand the basis for this response, we hypothesized that the proteins and peptides secreted by T. suis stimulate local intestinal epithelial cells to produce anti-inflammatory cytokines. To test this hypothesis in a correlate system of the natural swine host, T. suis excretory secretory products (ESP) were used to treat both differentiated and undifferentiated intestinal pig epithelial cells (IPEC-1) in vitro as a model for the effect on villus tip and crypt epithelial cells in the vicinity of the worms. IPEC-1 were exposed to low-level doses (0.3mg/ml) of T. suis ESP, and IL-4, IL-6 and IL-10 cytokine responses were measured by an enzyme-linked immunosorbant assay (ELISA). IL-6 was the predominant cytokine produced, accompanied by moderate IL-10 secretion from both differentiated and undifferentiated cells. As expected, IL-4 was not produced by IPEC-1. Additionally, IL-6 and IL-10 cytokines were produced within 24h, suggesting that these two cytokines form part of the primary host response to T. suis infections. These data suggest that T. suis ESP could enhance host immune responses and modulation through the induction of enteric IL-6 and IL-10.

  9. 多发性创伤后血清TNF-α、IL-1β、IL-6IL-10变化的连续观察%Continual observation of TNF-α,IL-1β,IL-6 and IL-10 in the plasma after severe multiple injury

    Institute of Scientific and Technical Information of China (English)

    张永和; 赵宁; 宋祖军

    2002-01-01

    探讨创伤患者TNF-α、IL-1β、IL-6IL-10血清浓度的变化及临床意义.方法 25例多发性创伤患者分别在受伤后第2、3、5、10及15天测定外周血清TNF-α、IL-1β、IL-6IL-10的变化,并与正常对照组进行对比分析.血清TNF-α浓度采用放免法测定,IL-1β、IL-6IL-10浓度采用酶联免疫吸附法测定.结果 TNF-α、IL-1β、IL-6IL-10血清浓度在多发性创伤后均较正常对照组显著增高,IL-1β及TNF-α于2周后恢复正常,而IL-6IL-10增高持续至2周后.结论 TNF-α、IL-1β、IL-6IL-10参与了多发性创伤病理生理过程,动态观察可能和病情程度有关.

  10. Does Toxoplasma gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha?

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    Joanna Matowicka-Karna

    2009-01-01

    Full Text Available In the study performed in a group of patients infected with T. gondii, we evaluated Th2 humoral response (IL-5, IL-6, IL-10 and Th1 cell response (IL-12, TNF-α. The study objective was to assess the effect of T. gondii on chosen indices of the immune response. The study involved 52 women infected with T. gondii (aged 18–42 years prior to antiparasitic treatment. In all the patients, we found IgM (index >0.7 and IgG which exceeded 300 IU/ml. The control group (C consisted of 40 healthy women aged 18–46 years. In the study group (T and in the control group (C, the levels of IgE, IL-5, IL-6, IL-10, IL-12, and TNF-α were determined. In our study, T. gondii patients had twofold higher levels of IL-5 and IL-6 as compared to healthy subjects, which seems to confirm the presence of an inflammatory state. We found the level of IL-10 to be fivefold higher in the course of toxoplasmosis than in healthy controls. The levels of IL-12 and TNF-α were comparable to those observed in healthy controls. The study has revealed that that patients infected with T. gondii show increased production of the humoral response cytokines, whereas the generation of the cell response cytokines remains unchanged.

  11. 急性颅脑损伤后血清IL-6IL-8IL-10含量变化及意义%The content change and significance of serum IL-6, IL-8 and IL-10 in patients with acute brain trauma

    Institute of Scientific and Technical Information of China (English)

    梁敏; 汤树洪; 甘渭河

    2013-01-01

    目的 探讨急性颅脑损伤后免疫功能紊乱的相关炎性介质与时间动态变化的关系,即血清中促炎细胞因子IL-6、IL-8和抗炎细胞因子IL-10 的含量变化及临床意义.方法 采用放射免疫分析法检测急性颅脑损伤患者150 例,分为轻、中、重型3组血清IL-6、IL-8、IL-10含量的变化,分析血清中IL-6、IL-8、IL-10含量之间的动态关系与急性颅脑损伤分级以及变化趋势.结果 重型组1 d、2 d、3 d、7 d、14 d5个时间点的IL-6、IL-8、IL-10水平较轻、中型明显升高;IL-6 水平于第2天达到最高峰,IL-8水平于第3天达到最高峰,IL-10水平于第7天达到最高峰;IL-6、IL-8、IL-10达到最高峰后均出现迅速下降趋势.结论 血清中IL-6、IL-8、IL-10 水平的变化与急性脑损伤程度呈正相关,即脑损伤程度越重,IL-6、IL-8、IL-10的水平越高.

  12. Serum IL-2, IL-6, IL-10 and TNF-α Levels in Patients with Vitiligo before and after Treatment%白癜风患者治疗前后血清IL-2、IL-6IL-10和TNF-α水平

    Institute of Scientific and Technical Information of China (English)

    孙岩; 钱立

    2011-01-01

    目的:探讨白癜风患者治疗前后血清IL-2、IL-6IL-10、和TNF-α水平及临床意义.方法:应用放射免疫分析法检测32例白癜风患者治疗前后血清IL-2、IL-6IL-10和TNF-α水平,以35名健康体检者为对照.结果:白癜风患者在治疗前血清IL-6IL-10、TNF-α水平非常显著地高于对照组(P<0.01),IL-2水平非常显著地低于对照组(P<0.01);经治疗3个月后与对照组比较仍有显著性差异(P<0.05),且血清IL-2水平与IL-6IL-10、TNF-α水平呈负相关(r=-0.482 2、-0.501 8、-0.613 4.P<0.01).结论:白癜风患者存在自身免疫调节的异常,检测血清IL-2、IL-6IL-10和TNF-α水平的变化对疾病的治疗和预后具有重要的临床价值.%Objective: To detect serum levels of IL-2, IL-6, IL-10, and TNF-a in patients with vitili-go and to investigate its clinical significance. Methods:Radioimmunoassay was adopted to detect serum levels of IL-2, IL-6, IL-10 and TNF-α of 32 patients with vitiligo before and after treatment. The results were compared with those of 35 healthy people. Results: Serum levels of IL-6, IL-10, TNF-a in vitiligo patients before treatment were significantly higher than those of healthy people ( P<0.01) , while IL-2 level was significantly lower than that of healthy people (P<0.01). After treatment for 3 months, the differences between the two groups were significant (P<0. 05 ) , and serum IL-2 level was negatively correlated with IL-6, IL-10 and TNF-a levels (r=-0.482 2, -0.5018, -0.613 4.P <0.01). Conclusion: Autoimmune regulation is abnormal in vitiligo patients. Detection of serum IL-2, IL-6, IL-10, IL-6 and TNF-a levels have important clinical value in treatment and prognosis of the disease.

  13. Role of IL-1ra/IL-1β and IL-10/IL-6 ratio in coronary artery disease%IL-1Ra/IL-1β及IL-10/IL-6比值在冠心病的作用及其意义

    Institute of Scientific and Technical Information of China (English)

    刘书院; 钟小理; 杨正林; 段克欣

    2012-01-01

    目的:探讨IL-1β、IL-1受体拮抗剂(IL-1 Ra)、IL-10IL-6水平及IL-1 Ra/IL-1β、IL-10/IL-6比值在冠状动脉粥样硬化性心脏病(冠心痛)患者血清中的变化以及临床意义.方法:选择稳定型心绞痛(SAP)患者26例,不稳定型心绞痛(UAP)患者27例,AMI患者27例,健康体检者30名,分为SAP组、UAP组、AMI组及正常对照组,采用ELISA法检测四组患者血清IL-1β、IL-1 Ra、IL-10IL-6水平,计算IL-1 Ra/IL-1β、IL-10/IL-6比值,并进行比较.结果:UAP组、AMI组患者的血清IL-1Ra水平均明显低于正常对照组(P<0.05),IL-1β高于对照组(P<0.05);三组冠心痛患者的IL-1 Ra/IL-1β比值均低于正常对照组(P<0.05).三组冠心病患者的血清IL-10IL-6水平均高于正常对照组(P均<0.05),而IL-10/IL-6比值低于正常对照组(P均<0.05).结论:IL-1β、IL-1Ra、IL-10IL-6可能参与了冠心病的炎症反应过程,IL-1Ra/IL-1β及IL-10/IL-6比值反映了冠心痛患者的免疫调节状况,其比值高低及动态变化对冠心痛患者的病情监测有重要参考价值.%Objective: To investigate the clinical significance of interleukin-1 β (IL-1β) , interleukin-1 recep- tor antagonist (IL-IRa) , interleukin 10 (IL-10) , interleukin-6 (IL-6) and the ratio of IL-1 Ra/IL-1 β, IL-10/IL-6 in coronary heart disease (CHD). Methods : Patients with stable angina pectoris (SAP group, n = 26), unstable angina pectoris ( UAP group, n = 26 ) , and acute myocardial infarction ( AMI group, n = 27) were involved. Thirty healthy people were selected as control group. Serum level of IL-1 β, IL-IRa, IL-10, IL-6 were detected by Enzyme-linked immunosorbent assay (ELISA) and the ratio of IL-1 Ra/IL-1 β and IL-10/IL-6 were calculated. Results : The serum level of IL-1 Ra in UAP group and AMI group were significantly lower , and IL-1β levels were significantly higher than that in control group (P <0. 05). IL-1 Ra/IL-1 p ratio in CHD patients was lower than in control group (P

  14. IL-1Ra对阿霉素肾病大鼠血清IL-6IL-10、IL-13、IL-1的影响%EFFECTS OF IL-1 RECEPTOR ANTAGONIST ON SERUM IL-6,IL-10,IL-13,AND IL-1 LEVELS IN ADRIAMYCIN NEPHROSIS IN RATS

    Institute of Scientific and Technical Information of China (English)

    林娜; 刘运广; 覃志坚; 李强

    2009-01-01

    目的:探讨IL-1Ra对阿霉素肾病大鼠血清IL-6IL-10、IL-13 、IL-1的影响.方法:将大鼠随机分为正常对照组(A组, n=10)、阿霉素肾病组(B组,n=10)、阿霉素肾病IL-1Ra治疗组(C组,n=10)、阿霉素肾病生理盐水治疗组(D组,n=10), 2周后检测尿24 hUP、血清IL-6IL-10、IL-13、IL-1、Al、T-ch、BUN、Scr.结果:B、C、D组血清IL-6IL-10、IL-13水平明显高于A组(P0.05).结论:IL-1Ra对阿霉素肾病大鼠有明显治疗作用的同时能提高抗炎细胞因子IL-6IL-10、IL-13的血清水平.

  15. Clinical significance of determination of serum IL-6,IL-10 and IL-13 levels in patients with mesangial proliferative glomerulonephritis%系膜增生性肾小球肾炎患者血清IL-6IL-10、IL-13检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    刘岩; 王桂成; 潘燕华

    2012-01-01

    目的 探讨系膜增生性肾小球肾炎治疗前后血清IL-6IL-10、IL-13水平的变化及意义.方法 测定70例患者治疗前后血清IL-6IL-10、IL-13的含量,并与30例正常健康者作比较.结果 激素敏感组系膜增生性肾小球肾炎患者在治疗后血清IL-6IL-10、IL-13水平较治疗前降低(P<0.05).结论 血清IL-6IL-10、IL-13水平变化在一定程度上可提示病情变化,监测治疗效果.

  16. 急性结膜炎患者治疗前后血清hs-CRP、IL-6IL-10、IL-18检测的临床意义%Clinical Significance of Determination of Changes in Serum hs-CRP, IL-6,IL-10,and IL-18 Levels After Treatment in Patients with Acute Conjunctivitis

    Institute of Scientific and Technical Information of China (English)

    刘钧

    2007-01-01

    目的:探讨了急性结膜炎患者治疗前后血清hs-CRP、IL-6IL-10、IL-18水平的变化及意义.方法:分别应用放免法、免疫比浊法和酶联法对38例急性结膜炎患者进行了血清hs-CRP、IL-6IL-10和IL-18水平检测,并与35名正常健康人作比较.结果:急性结膜炎患者在治疗前血清hs-CRP、IL-6IL-10和IL-18水平均非常显著地高于正常人(P<0.01),经2周的抗炎治疗后则与正常人比较无显著性差异(P>0.05).结论:检测急性结膜炎患者血清hs-CRP、IL-6IL-10和IL-18水平的变化对临床观察预后有重要的临床价值.

  17. Clinical Significance of Determination of Changes of Serum of TNF-α, IL-6, IL-8,IL-10 Levels After Treatment in Patients with Condyloma Acuminatum%尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王亚平

    2007-01-01

    目的:探讨了尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10水平变化及意义.方法:应用RIA和ELISA对40例尖锐湿疣患者进行了血清TNF-α、IL-6、IL-8、IL-10水平检测并与35名正常健康人作比较.结果:在治疗前尖锐湿疣患者血清IL-6及IL-8低于正常对照组.TNF-α、IL-10水平均非常显著地高于正常对照组(P<0.01),经治疗3个月后与正常对照组比较仍有显著性差异(P<0.05).结论:检测尖锐湿疣患者血清TNF-α、IL-6、IL-8、IL-10水平的变化对疾病的治疗、预后观察有重要的临床价值.

  18. STUDY ON THE CONTENT OF IL- 6 AND IL- 10 IN GCF BEFORE AND AFTER BASIC TREATMENT OF PERIODONTITIS%牙周炎龈沟液中IL-6IL-10水平变化与临床指标关系的研究

    Institute of Scientific and Technical Information of China (English)

    李云华; 李丽洁

    2012-01-01

    Objective: To explore the changes of clinical markers and content in the Interleukin -6( IL -6) ,interleukin - 10( IL - 10) levels before and after the periodontal treatment 6,8, 10wk of gingival crevicular fluid (GCF) with periodontitis. Methods: Collected gingival crevicular fluid from 40 healthy teeth with healthy people; Mild and severe periodontitis groups of 40 teeth of the GCF inflammatory. Using enzyme -linked immunosorbent assay( ELISA)to detect the IL -6 and IL - 10 levelsin GCF,and record the probing depth(PD) ,attachment loss(CAL) ,plaque index( PLI) and gingival sul-cus bleeding index(SBI) ,before and after treatment 6,8,10wk,analyzing their relevance. Results:Before and after treatment, IL - 6 levels in GCF of periodontitis patients were significantly higher than healthy controls(P<0. 01 ) ;IL -6 levels in GCF of severe periodontitis were higher than those with mild periodontitis group(P <0. 01 ). After periodontal therapy,the IL -6 of periodontitis group were significandy reduced. PD, AL, PLI and SBI were positive correlation( P < 0. 05 ) , while IL - 10 of GCF in patients with periodontitis was significantly lower than healthy controls( P <0.01) , IL - 10 of GCFin patients with severe periodontitis was lower than in patients with mild periodontitis ( P <0. 01 ). After periodonta] therapy, the IL - 10 of periodontitis group were significantly increased. PD, AL,PLI and SBI was negatively correlated (P <0. 05) ,IL -6 and IL - 10 are in the corresponding negative correlation between time points (P < 0. 05 ). Conclusion: IL - 6 levels after treatment is a gradual decrease in 10wk,while the IL - 10 levels is gradually increased in 10wk,in the corresponding time point the two factors IL -6 and IL - 10 are negative correlation.%目的:探讨牙周炎病人牙周基础治疗前及治疗后6wk、8wk、10wk龈沟液(gingival crevicular fluid,GCF)中白细胞介素-6(interleukin -6,IL -6)、白细胞介素- 10(interleukin - 10,IL - 10)含量及相关临床指

  19. 高通量血液透析对血透患者IL-10IL-6及hs-CRP水平的影响%Effects of High-flux Hemodialysis on Level of IL-10 ,IL-6 and hs-CRP in Maintenance Dialysis Patients

    Institute of Scientific and Technical Information of China (English)

    濮红梅; 尹忠诚; 刘秉成

    2012-01-01

    Objective To investigate the effects of high-flux hemodialysis on plasma interleukin-10(IL-10) , interleukin-6 (IL-6) and high sensitive C-reactive protein( hs-CRP) in maintenance dialysis( MHD) patients. Methods Thirty-two MHD patients were randomly divided into two groups,and treated by using the high-flux hemo- dialysis( HFHD) and low-flux hemodialysis ( LFHD) with dialyzer of polysulfone membranes. The plasma levels IL-10,IL-6 and hs-CRP before and after the dialysis was measured in the two groups and fourteen healthy controls. Results The plasma levels of IL-10, IL-6 and hs-CRP before and after the dialysis in both dialysis groups were significant elevated as compared to control groups (P 0.05),those parameters after the dialysis increase significantly in patients with LFHD as compared to its levels before dialysis ( P 0.05). Conclusion Inflammatory cytokines were significantly higher in MHD patients. HFHD cannot lead to elevate inflammatory cytokines and,consequently,is considered to be the better renal replacement therapy.%目的 探讨高通量血液透析对维持性血液透析(MHD)患者血浆白细胞介素-10(IL-10)、白细胞介素-6(IL-6)、高敏C-反应蛋白(hs-CRP)水平的影响.方法 将32例MHD患者随机分为两组,采用聚砜膜分别进行高通量血液透析(HFHD)与低通量血液透析(LFHD),测定其透析前后的血浆IL-10IL-6、hs-CRP的水平;同时选择14例健康志愿者作为对照组.结果 HFHD组、LFHD组透析前IL-10IL-6和hs-CRP的血浆水平均显著高于对照组(P<0.05);HF-HD组透析后IL-10IL-6、hs-CRP的血浆水平与透析前相比差异均无统计学意义(P>0.05),LFHD组透析后IL-10IL-6和hs-CRP的血浆水平均显著高于透析前(P<0.05);HFHD组与LFHD组透析后IL-10IL-6和hs-CRP的血浆水平比较差异均无统计学意义(P>0.05).结论 MHD患者存在血浆IL-10IL-6和hs-CRP水平的异常增高,HFHD未升高血浆炎性细胞因子的水平,是目前较好的血液净化技术.

  20. Blood concentrations of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma during experimentally induced swine dysentery

    Directory of Open Access Journals (Sweden)

    Jensen-Waern Marianne

    2008-08-01

    Full Text Available Abstract Background Knowledge of the cytokine response at infection with Brachyspira hyodysenteriae can help understanding disease mechanisme involved during swine dysentery. Since this knowledge is still limited the aim of the present study was to induce dysentery experimentally in pigs and to monitor the development of important immunoregulatory cytokines in blood collected at various stages of the disease. Methods Ten conventional pigs (~23 kg were orally inoculated with Brachyspira hyodysenteriae B204T. Eight animals developed muco-haemorrhagic diarrhoea with impaired general body condition. Blood was sampled before inoculation and repeatedly during acute dysentery and recovery periods and cytokine levels of IL-1β, IL-6, Il-10, TNF-α and IFN-γ were measured by ELISA. Results IL-1β was increased at the beginning of the dysentery period and coincided with the appearance of Serum amyloid A and clinical signs of disease. TNF-α increased in all animals after inoculation, with a peak during dysentery, and IL-6 was found in 3 animals during dysentery and in the 2 animals that did not develop clinical signs of disease. IL-10 was found in all sick animals during the recovery period. IFN-γ was not detected on any occasion. Conclusion B. hyodysenteriae inoculation induced production of systemic levels of IL-1β during the dysentery period and increased levels of IL-10 coincided with recovery from dysentery.

  1. Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

    Institute of Scientific and Technical Information of China (English)

    Lei ZHANG; Jing-yong ZHOU

    2008-01-01

    Objective To investigate the correlation of interleukin(IL)-1,IL-6 and IL-10 concen-trations to ovarian hyperstimulation syndrome(OHSS) and whether intravenousimmunoglobulin(IVIG) has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group,OHSS group (n=13)and IVIG group(n=13).For the latter two groups,pregnancy mare serum gonadotropin(PMSG)and human chorionic gonadotropin(hCG)were given to induce OHSS,and rats in IVIG group were treated with immunoglobulin.Forty—eight hours after administration of hCG,capillary permeability was evaluated from the Evans blue dye(EB) concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB.Rats’blood samples and ovaries were obtained to be measured for IL-1,IL-6 and IL-10 by ELISA.Results In OHSS group,total weights of bilateral ovaries and the ovarian EB concen—tration were significantly higher than those in others(P<0.05).Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group (P<0.05).The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group(P<0.05).Furthermore,the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group(P<0.05). Conclusion Inflammation involved IL-1 in OHSS rats plays an important role.Vascular permeability was mostly increased in ovaries of hyperstimulated rats.It appears that ovaries of OHSS rats may be the primary places of inflammation.IVIG treatment resulted in statistically significant reductions in ovaries’weights and ovarian vascular permeability of OHSS rats,with a decreased level of ovarian IL-10.It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

  2. Study on the Changes of Serum IL-6 ,IL-8 and IL-10 Levels in Patients with Chronic Hepatitis and its Clinical Significance%慢性肝炎患者血清IL-6、IL-8、IL-10的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刁慕言

    2006-01-01

    目的探讨慢性肝炎患者血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)在慢性肝炎发展过程中的含量变化及其临床意义.方法用放射免疫分析法检测80例慢性肝炎患者和40例正常对照组血清IL-6、IL-8和IL-10的水平.结果各组慢性肝炎患者血清IL-6和IL-8含量高于正常对照组,差异有统计学意义(P<0.05);IL-10低于正常对照组,差异有统计学意义(P<0.01).IL-6、IL-8和IL-10水平的变化与慢性肝炎病变程度密切相关.结论细胞因子IL-6、IL-8和IL-10在慢性肝炎发展过程中相互作用,联合检测其水平的变化对探讨慢性肝炎的诊断和预后具有重要意义.

  3. Clinical significance of the Changes of Serum Levels of IL-2,IL-6,IL-10,IL-18 and T cell subset in patients with chronic nephritis%慢性肾炎治疗前后血清IL-2、IL-6IL-10、IL-18和T淋巴细胞亚群检测意义

    Institute of Scientific and Technical Information of China (English)

    刘薇娜; 鲍培玉; 蒋全

    2010-01-01

    目的 探讨慢性肾炎患者治疗前后血清IL-2、IL-6IL-10、IL-18和T淋巴细胞亚群的变化.方法 分别应用放免法、ELISA法和单克隆抗体法对30例慢性肾炎患者治疗前后进行了血清IL-2、IL-6IL-10、IL-18和T淋巴细胞亚群水平的检测,并与35名正常健康人作比较.结果 慢性肾炎患者在治疗前血清IL-2和CD4/CD8比值明显低于正常人组(P<0.05),而IL-6IL-10和IL-18水平高于正常人组(P<0.01);经半年治疗后血清IL-2、IL-6IL-10、IL-18和CD4/CD8与治疗前组比较差异有统计学意义(P<0.05).结论 检测慢性肾炎患者血清IL-2、IL-6IL-10、IL-18和T淋巴细胞亚群水平对判断病情及其预后均具有一定的临床实用价值.

  4. Application value of serum TNF-α, IL-6, IL-8, IL-10 in children mycoplasma pneumoniae pneumonia%血清TNF-α、IL-6、IL-8、IL-10在儿童肺炎支原体肺炎中的应用价值

    Institute of Scientific and Technical Information of China (English)

    李锦; 郭瑞雪; 王金虎

    2015-01-01

    目的:对血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)浓度在儿童肺炎支原体肺炎(MPP)中的应用价值进行探讨。方法90例肺炎支原体肺炎患儿作为肺炎组,其中轻症组50例,重症组40例;100例健康体检儿童作为对照组,对比肺炎组与对照组血清TNF-α、IL-6、IL-8和IL-10指标及轻症组与重症组血清中的各因子浓度。结果对照组与肺炎组治疗前血清中TNF-α、IL-6、IL-8和IL-10浓度差异具有统计学意义(P0.05), TNF-α、IL-6及IL-8浓度均显著低于重症组,差异具有统计学意义(P0.05). They had much lower TNF-α, IL-6, IL-8 than the severe group, and their differences had statistical significance (P<0.05).Conclusion Serum TNF-α, IL-6, IL-8, IL-10 have certain correlation with mycoplasma pneumoniae pneumonia, and they are closely correlated with MPP degree. They can be used as evaluation indexes for clinical diagnosis, treatment and prognosis.

  5. 糖尿病周围神经病变患者 IL-6IL-10水平与神经纤维损伤程度的相关性分析

    Institute of Scientific and Technical Information of China (English)

    蔡文婷; 李小毅; 毛春谱

    2016-01-01

    目的:探讨糖尿病周围神经病变患者 IL-6IL-10水平与神经纤维损伤程度的相关性。方法选取2013-01—2015-01我院收治的2型糖尿病患者100例,根据血清 IL-6IL-10表达水平将患者分为 IL-6+组和 IL-6-组,以及 IL-10+组和 IL-10-组。比较不同血清 IL-6IL-10表达水平的糖尿病周围神经病变患者的临床资料、电生理检测结果以及温度感觉检测结果。结果IL-6+组患者血清糖化血红蛋白浓度明显高于 IL-6-组(P <0.05);IL-6+组患者腓肠神经 SNAP 振幅以及腓总神经 CMAP 振幅明显低于 IL-6-组(P <0.05),IL-10+组患者腓肠神经 SNAP 振幅以及腓总神经 CMAP 振幅、MNCV、F波最小潜伏期均明显低于 IL-10-组(P <0.05);IL-6+组 WDT 明显高于 IL-6-组(P <0.05);IL-10+组 WDT 明显高于 IL-10-组(P <0.05),IL-10+组 CDT 明显低于 IL-10-组(P <0.05)。结论血清 IL-6IL-10表达水平与糖尿病周围神经病变患者神经纤维损伤程度有相关性,细胞因子 IL-6IL-10可能在糖尿病周围神经病变发生过程中发生作用。

  6. 手足口病患儿血清中IL-6 IL-10 IL-13及IL-17的变化及临床意义%Changes and clinical significance of serum IL-6,IL-10,IL-13 and IL-17 levels in children with hand-foot-mouth disease

    Institute of Scientific and Technical Information of China (English)

    陈笑辉; 樊冰

    2013-01-01

    Objective To study the changes and clinical significance of serum IL-6,IL-10,IL-13,IL-17 levels in the children with hand-foot-mouth disease (HFMD).Methods The serum concentration of IL-6,IL-10,IL-13,IL-17 in 46 case of HFMD children with acute stage and recovery stage and 40 cases of healthy controls were measured by ELISA.The data was analyzed by statistical SPSS software.Results In acute stage,the levels of IL-6,IL-10,IL-13,IL-17 in children of severe HFMD were higher than those in general children (P<0.01),showing significant difference from those in healthy controls (P<0.01).In recovery stage,the levels of IL-6 and IL-17 of HFMD were significantly lower than those in acute stage,and also no significant difference showed from those in general children and in healthy controls (P>0.05).Conclusion The levels of IL-6 and IL-17 were significantly increased in acute stage of HFMD children.The persistent elevation of serum IL-10 and IL-13 levels were found in HFMD patients after convalescence.%目的 探讨手足口病患儿血清中IL-6 IL-10 IL-13及IL-17的变化及临床意义.方法 采用酶联免疫吸附实验(ELISA)抗体夹心法测定46例手足口病患儿急性期、恢复期及40例健康体检儿童血清IL-6IL-10、IL-13、IL-17的含量,对手足口病患儿急性期、恢复期进行比较,同时对其中重症患儿、普通患儿进行比较,用统计软件进行统计学分析.结果 急性期重症组与普通组IL-6IL-10、IL-13及IL-17水平均明显升高,与对照组比较有统计学意义(P<0.01),重症组与普通组比较有统计学意义(P<0.01).恢复期重症组与普通组IL-6、IL-17较急性期下降,普通组与对照组比较无统计学意义(P>0.05),而重症组与对照组比较有统计学意义(P<0.01),但是IL-10、IL-13重症组和普通组均较急性期下降,但仍高于对照组,两组与对照组比较有统计学意义(P<0.01).结论 炎症因子IL-6、IL-17在急性期水平显著升高,而抑制性细胞因子IL

  7. Clinical significance on the changes of serum IL-6,IL-8 and IL-10 levels in children with H.pylori infection%幽门螺杆菌感染患儿血清 IL-6、IL-8、IL-10水平变化

    Institute of Scientific and Technical Information of China (English)

    陈一; 阎晓莉; 李华; 拜康利

    2003-01-01

    为探讨各种细胞因子在幽门螺杆菌相关性胃肠粘膜病中的作用机理及意义,采用 ELISA法,检测 35例幽门螺杆菌阳性患儿血清 IL-6、 IL-8、 IL-10水平,并与幽门螺杆菌阴性组 31例作对照.结果显示两组间 IL-6、 IL-8分布水平差异有极显著性( P<0.001);两组间 IL-10分布水平差异有显著性( P<0.05).幽门螺杆菌阳性组与阴性组 IL-6平均秩和之差为 16.38,均数分别为 108.46pg/ml及 51.32pg/ml; IL-8平均秩和之差为 34,均数分别为 163.09pg/ml及 92.36pg/ml; IL-10平均秩和之差为- 3.32,均数分别为 12.56pg/ml及 15.88pg/ml.幽门螺杆菌阳性组血清 IL-6与 IL-8间呈正相关( r=0.349, P<0.001); IL-10IL-6、 IL-8间无明显相关性.提示细胞因子 IL-6、 IL-8、 IL-10均参与了幽门螺杆菌感染后的致病过程;幽门螺杆菌感染胃肠粘膜产生的炎症反应损伤与 IL-6、 IL-8的过量产生有关,血清 IL-10对炎症有抑制作用,从而为临床诊治幽门螺杆菌相关性疾病提供理论依据.

  8. ICH 患者血清和血肿液中 IL-4、IL-6、IL-8、IL-10的变化研究%Hematoma fluid and serum of patients with acute cerebral hemorrhage about IL-4, IL-6, IL-8, and IL-10 Changes

    Institute of Scientific and Technical Information of China (English)

    赵金安; 白西民

    2016-01-01

    目的:观察急性脑出血(ICH)患者血清和血肿液中 IL-4、IL-6、IL-8、IL-10的变化。方法:选取80例在我院治疗的基底节区脑出血患者,按照发病时间将患者分为5组(发病时间≤6h、6h <发病时间≤12h、12h <发病时间≤24h、24h <发病时间≤72h、3d <发病时间≤7d),检测各组血清和血肿液中 IL-4、IL-6、IL-8、IL-10的含量以及出血量和水肿量;另选取21例健康体检者,检测其血清 IL-4、IL-6、IL-8、IL-10的含量作对照。结果:IL-4、IL-6、IL-8、IL-10在患者静脉血、血肿液中的浓度均显著高于正常对照组,而患者静脉血与血肿液中 IL-4、IL-6、IL-8、IL-10浓度比较,差异无统计学意义。基底节区脑出血患者发病时间≤6h 与正常对照组比较,除 IL-10浓度升高不明显外,IL-4、IL-6、IL-8浓度均明显升高;24h <发病时间≤72h 时,IL-4、IL-6、IL-8浓度与其他各时段比较,以及3d <发病时间≤7d时,IL-10浓度与其他各时段比较,差异均具有统计学意义。各时段出血量和水肿量比较,差异均无统计学意义,出血量和水肿量均在发病时间≤6h至12h <发病时间≤24h 逐渐增大,12h <发病时间≤24h 达到峰值。结论:ICH 患者静脉血、血肿液中 IL-4、IL-6、IL-8浓度可以作为早期检测(≤6h)ICH 的指标,并可通过不同炎症因子的含量变化判断 ICH 患者发病时间,且患者发病一周内周围脑组织出血量和水肿量变化不大。%Objective To observe the changes of IL-4, IL-6, IL-8, IL-10 in serum and hematoma of ICH. Methods 80 cases ICH patients were divided into five groups(<6h, 6-12h, 12-24h, 24-72h, 3-7d). The control group were 21 healthy persons serum. The content of IL-4, IL-6, IL-8, IL-10 in different time were compared and the amount of bleeding and edema. Results IL-4, IL-6, IL-8, IL-10 in patients with venous hematoma fluid concentrations were

  9. 溃肠宁对TNBS模型大鼠肠形态、血清及结肠组织IL-6IL-10影响的观察%Observations on the influences of Kuichangning on morphology, serum and colonic IL-6, IL-10 in TNBS-induced ulcerative colitis rats

    Institute of Scientific and Technical Information of China (English)

    甘爱萍; 唐熙婷; 杨光英

    2014-01-01

    [目的]观察中药溃肠宁对三硝基苯磺酸(TNBS)致溃疡性结肠炎(UC)大鼠模型肠黏膜形态、大鼠血清及结肠黏膜组织中白介素-6(IL-6)、白介素-10(IL-10)表达的影响,探讨溃肠宁抗UC的相关作用机制以及疗效.[方法]采用TNBS复合50%乙醇法复制UC大鼠模型,分别采用中药溃肠宁和柳氮磺胺毗啶(SASP)作为阳性对照组进行治疗,对比模型组和空白对照组采用ELISA法对各组大鼠肠血清以及肠黏膜中IL-6IL-10进行检测,并对其检测结果进行分析.[结果]模型组大鼠结肠和血清中的IL-6含量明显高于正常组(P<0.01),IL-10的含量则明显低于正常组(P<0.01);SASP组结肠及血清中IL-6IL-10含量与模型组比较差异有统计学意义(P<0.01);中药组和模型组相比,结肠和血清中IL-6含量明显低于模型组(P<0.01),IL-10的含量则明显高于模型组(P<0.01);中药组与西药SASP组比较,中药组结肠和血清中IL-6含量低于西药组,IL-10的含量高于西药组,可见2组之间差异有统计学意义(P<0.01).[结论]溃肠宁对TNBS复合50%乙醇法UC大鼠疗效显著,其作用机制可能与调节机体的免疫有关.

  10. The Study of BALF TNF-α,IL-6,IL-8,IL-10 Concentration in Critically Ill Pneumonia Mycoplasma Pneumonia Patients%重症肺炎支原体肺炎肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平观察

    Institute of Scientific and Technical Information of China (English)

    叶新明; 钱克俭

    2010-01-01

    目的 检测重症肺炎支原体肺炎患者支气管肺泡灌洗液(bronchial tube pulmonary alveolus syringe fluid,BALF)中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)白细胞介素-10(Interleukin-10,IL-10)浓度,探讨其临床意义.方法 收住ICU的重症肺炎支原体肺炎患者36例,其CPIS评分>6分为CPIS高分组共15例,CPIS评分<6分为CPIS低分组共21例;正常对照组24例.取支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平.结果 重症肺炎支原体肺炎无论CPIS高分组和CPIS低分组支气管肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平明显高于对照组,差异有统计学意义(P0.05).2组治疗后恢复期TNF-α、IL-6、IL-8、IL-10水平均明显下降(P<0.01).结论 TNF-α、IL-6、IL-8、IL-10在重症肺炎的发生发展中起重要作用,是重症肺炎支原体肺炎诊断的重要因素之一.利用支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平变化对临床诊断治疗及预后有一定的临床价值.

  11. Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis.

    Science.gov (United States)

    Mao, Zheng-Rong; Zhang, Shao-Lei; Feng, Bo

    2017-03-01

    Association between inherited variants and the risks of sepsis is controversial. To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10. Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls. Subjects with IL-10 -1082 AA genotypes and IL-6 -174 CC genotype had a higher risk of sepsis and increased mRNA levels. The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.

  12. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

    Science.gov (United States)

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T; Huang, Ying; Xu, Lijun; Zhou, Qihui; Zhu, Biao

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  13. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia

    Directory of Open Access Journals (Sweden)

    Jia Sun

    2016-01-01

    Full Text Available Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P=0.008, R2=0.258, HBDH (P=0.001, R2=0.335, and Ferritin (P=0.005, R2=0.237. Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P<0.001; 1.11 ± 0.72, P=0.043, larger AUC (95% CI 0.781–1.000, P<0.001; 95% CI 0.592–0.917, P=0.043, and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  14. 分娩镇痛后产妇血清IL-6、IL-8、IL-10的变化%Effect of analgesia with continued epidural block on the serum IL-6, IL-8 and IL-10 in parturients

    Institute of Scientific and Technical Information of China (English)

    修玉芳; 黄东林; 王颖; 肖龙

    2013-01-01

    目的:观察罗哌卡因连续硬膜外阻滞进行分娩镇痛对产妇血清中IL-6、IL-8、IL-10的影响.方法:将200例产妇随机分为观察组和对照组各100例.观察组在宫口开至2 ~3 cm时,开始采用连续硬膜外阻滞进行分娩镇痛;对照组按产科常规处理.观察两组产妇分娩镇痛前30 min、分娩镇痛后2h、分娩后24 h、48 h和72 h等5个时点的IL-6、IL-8、IL-10水平的变化.结果:两组产妇分娩镇痛后血清IL-6、IL-8、IL-10水平与分娩镇痛前比较均有升高(P<0.01),且多在分娩后24 h达峰值,对照组较观察组升高更为明显(P<0.05).结论:罗哌卡因连续硬膜外阻滞进行分娩镇痛可有效降低产妇分娩后炎性应激反应.%Objective:To observe the effect of labor analgesia with continued epidural block on the serum IL-6,IL-8 and IL-10 in parturients.Methods:Two hundreds of labor women were divided into two groups with 100 cases each group.One hundred parturients were selected as labor analgesia group (group I) and the others were as nature delivery group without analgesia (group II).Analgesia was used when utero-cervical was opened to 2 ~ 3 cm.The levels of serum IL-6,IL-8 and IL-10 were observed at five time points:before labor analgesia,at 2 h after the labor analgesia,at 24,48,72 h after delivery.Results:The levels of serum IL-6,IL-8 and IL-10 were increased significantly after labor analgesia,reached at peak values at 24 h (P < 0.05),and then gradually declined but still higher than the baseline values.The serum IL-6,IL-8 and IL-10 were significantly higher at 2 and 24 h in group Ⅱ than those in group I (P < 0.05).Conclusion:Labor analgesia with continued epidural block is safe and effective.Epidural analgesia can reduce the level of serum IL-6,IL-8 and IL-10 and inflammatory response during delivery.

  15. 外源性IL-10对小儿牙龈炎组织中IL-6和细胞间黏附分子-1表达的影响研究%Study on the effect of exogenous IL-10 on IL-6 and intercellular adhesion molecule-1 expressions in gingivitis tissue of children

    Institute of Scientific and Technical Information of China (English)

    牛兵; 姜瑞中; 王国芳

    2015-01-01

    目的 研究外源性IL-10对小儿牙龈炎组织中IL-6和细胞间黏附分子-1 (ICAM-1)表达的影响.方法 选取2012年5月~2014年6月在该院接受治疗的80例牙龈炎患儿和正常进行健康检查的儿童40名为研究对象.根据探诊深度及附着丧失实施分组,轻度牙龈炎组简称轻度组、重度牙龈炎组简称重度组,各40例,选取同期在该院进行健康检查的儿童40名为对照组.对比各组IL-6含量水平,各组ICAM-1含量水平,分析外源性IL-10IL-6及ICAM-1的相关性.结果 重度组IL-6含量水平均高于其他两组,经过治疗后重度组及轻度组的IL-6含量水平均降低,但治疗7天后仍显著高于对照组的水平,差异均有统计学意义(均P<0.05).重度组的ICAM-1含量水平均分别显著高于轻度组和对照组,经过治疗后,重度组及轻度组的ICAM-1含量水平均降低,但治疗7天后仍显著高于对照组的水平,差异均有统计学意义(均P<0.05).通过Spearman法分析相关性可知,外源性IL-10IL-6及ICAM-1均呈显著负相关.结论 外源性IL-10能够较好地降低小儿牙龈炎组织关于IL-6及ICAM-1的表达,值得临床进一步深入研究.

  16. Change of IL-1β, IL-6, IL-8 ,TNF-α, IL-10 in cerebrospinal fluid after brain injury and its clinical significance%脑外伤患者脑脊液IL-1β、IL-6、IL-8、TNF-α、IL-10水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    吕丽霞; 张玲; 韩媛; 张国栋; 李巍; 杨萍; 张飚

    2013-01-01

    目的 探讨脑外伤时不同时期脑脊液IL-1β、IL-6、IL-8、TNF-α、IL-10的水平变化及临床意义.方法 选择48例脑外伤患者,其中重型26例、轻型22例;高颅内压25例、低颅内压23例.分别留取伤后12、24、36、72 h的脑脊液标本,采用酶联免疫吸附法检测伤后各时间点脑脊液IL-1β、IL-6、IL-8、TNF-α、IL-10水平.另取查体健康者28例为对照组.结果 与对照组相比,脑外伤患者脑脊液中IL-6、IL-1β、TNF-α、IL-8和IL-10水平均显著增高(P均<0.01).脑外伤重型组脑脊液IL-6、IL-1β、TNF-α和IL-8峰值水平高于与轻型组(P均<0.01);高颅内压组脑脊液中IL-1β峰值水平高于低颅内压组(P<0.01).结论 脑外伤后脑脊液炎性细胞因子水平升高,可作为预测脑损伤严重程度的指标.%Objective To investigate the concentration change of the inflammatory cytokines (IL-1 β,IL-6,IL-8,TNF-α,IL-10) in cerebrospinal fluid at different periods of time after traumatic brain injury.Methodds In this study,48 patients with traumatic brain injury were enrolled,the cerebrospinal fluid samples were collected in 12 h,24 h,36 h and 72 h after traumatic brain injury,the concentration of the inflammatory cytokines were detected with enzyme-linked immunosorbent assay.Results Compared with that in control group,there were significantly increased concentrations of IL-1 β,IL-6,IL-8,TNF-α,IL-10 in patients with traumatic brain injury(all P < 0.01).Peak concentrations of IL-6,IL-1 β,TNF-α and IL-8 of cerebrospinal fluid in patients with severe brain injury were significantly higher than those in patients with mild brain injury(all P < 0.01).Peak concentration of IL-1 β in patients with high intracranial pressure was higher than that in patients with low intracranial pressure(P <0.01).Conclusion The levels of IL-1 β,IL-6,IL-8,TNF-α and IL-10 increase after the traumatic brain injury,which may be one of the probable biomarkers for the severity

  17. Identification of BCAP-{sub L} as a negative regulator of the TLR signaling-induced production of IL-6 and IL-10 in macrophages by tyrosine phosphoproteomics

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Takayuki [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Oyama, Masaaki; Kozuka-Hata, Hiroko [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Ishikawa, Kosuke; Inoue, Takafumi [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Muta, Tatsushi [Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578 (Japan); Semba, Kentaro, E-mail: ksemba@waseda.jp [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan)

    2010-09-17

    Research highlights: {yields} Twenty five tyrosine-phosphorylated proteins in LPS-stimulated macrophages were determined. {yields} BCAP is a novel tyrosine-phosphorylated protein in LPS-stimulated macrophages. {yields} BCAP-{sub L} inhibits IL-6 and IL-10 production in LPS-stimulated macrophages. -- Abstract: Toll-like receptor (TLR) signaling in macrophages is essential for anti-pathogen responses such as cytokine production and antigen presentation. Although numerous reports suggest that protein tyrosine kinases (PTKs) are involved in cytokine induction in response to lipopolysaccharides (LPS; TLR4 ligand) in macrophages, the PTK-mediated signal transduction pathway has yet to be analyzed in detail. Here, we carried out a comprehensive and quantitative dynamic tyrosine phosphoproteomic analysis on the TLR4-mediated host defense system in RAW264.7 macrophages using stable isotope labeling by amino acids in cell culture (SILAC). We determined the temporal profiles of 25 proteins based on SILAC-encoded peptide(s). Of these, we focused on the tyrosine phosphorylation of B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) because the function of BCAP remains unknown in TLR signaling in macrophages. Furthermore, Bcap has two distinct transcripts, a full-length (Bcap-{sub L}) and an alternatively initiated or spliced (Bcap-{sub S}) mRNA, and little is known about the differential functions of the BCAP-{sub L} and BCAP-{sub S} proteins. Our study showed, for the first time, that RNAi-mediated selective depletion of BCAP-{sub L} enhanced IL-6 and IL-10 production but not TNF-{alpha} production in TLR ligand-stimulated macrophages. We propose that BCAP-{sub L} (but not BCAP-{sub S}) is a negative regulator of the TLR-mediated host defense system in macrophages.

  18. B-cell exposure to self-antigen induces IL-10 producing B cells as well as IL-6- and TNF-α-producing B-cell subsets in healthy humans

    DEFF Research Database (Denmark)

    Langkjær, Anina; Kristensen, Birte; Hansen, Bjarke E

    2012-01-01

    of IL-10 and TGF-β, in addition to TNF-α and IL-6. Pulsing with foreign antigen, tetanus toxoid (TT), induced a Th1-response with minimal IL-10 production. After thyroglobulin-pulsing, 1.10±0.50% of B cells and 1.00±0.20% of CD4(+) T cells produced IL-10, compared to 0.29±0.19% of B cells (P=0.01) and 0...

  19. 符合全身炎症反应综合征的上呼吸道感染患儿IL-6IL-10的变化

    Institute of Scientific and Technical Information of China (English)

    谷强; 杨军; 杨红; 陈志刚

    2005-01-01

    目的 观察符合全身炎症反应综合征(SIRS)诊断的急性上呼吸道感染患儿血浆IL-6IL-10IL-6IL-10的变化。方法 采用酶联免疫吸附法测定符合SIRS诊断的19例上呼吸道感染患儿入院时及5~7天后IL-6IL-10的变化并与15例正常对照组进行比较。结果 上呼吸道感染患儿入院时IL-6IL-10分别为(142.97±165.53)pg/ml、(50±56.93)pg/ml较正常对照组(13.15±20.33)pg/ml、(7.33±7.32)pg/ml升高,P值分别为0.00355、0.0052,体温正常,5~7天后复查IL-6降低,IL-10仍偏高,IL-6IL-10比值降低。结论 IL-6IL-10参与了上呼吸道感染患儿炎症反应的发生、发展和转归。

  20. 糖尿病合并高血压患者血清 IL-6IL-10、TNF-α水平变化及意义

    Institute of Scientific and Technical Information of China (English)

    张华; 刘利祥; 刘智

    2015-01-01

    目的:观察糖尿病合并高血压患者血清促炎细胞因子( IL-6、TNF-α)和抗炎细胞因子( IL-10)水平变化,并探讨其意义。方法糖尿病合并高血压患者52例( A组)、单纯糖尿病患者61例( B组)、单纯高血压患者40例( C组)、成年健康者40例( D组),采用化学发光法检测各组血清IL-6IL-10、TNF-α,并计算IL-6IL-10、TNF-α/IL-10值。结果 D、C、B、A组血清IL-6、TNF-α水平逐渐升高,各组比较,P均<0.05。与B组相比,A组血清IL-10水平高,IL-6IL-10、TNF-α/IL-10值低(P均<0.05)。结论血清IL-6、TNF-α、IL-10水平升高预示糖尿病患者具有并发高血压风险。

  1. Effect of dexmedetomidine on the survival rate and serum level of IL-6 and IL-10 in rats with sepsis%右美托咪定对脓毒血症大鼠生存率和血清IL-6IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    王益兵; 曹东航; 周春莲; 陈跃; 王明仓

    2015-01-01

    Objective To study the effect of dexmedetomidine on the survival rate and serum level of IL-6 and IL-10 in rats with sepsis. Methods A total of 30 wistar rats were chosen and randomly divided into three groups: 10 rats in group saline (Group S), 10 rats in group dexmedetomidine (Group D) and 10 rats in group endotoxin (Group E). The survival rate, level of IL-6 and IL-10 and apoptosis rate of lymphocyte were compared. Results After 6 hours, the survival rate of group S, group E and group D were 100.00%, 30.00% and 90.00% respectively. And the survival rate of group E was significantly lower than group S and group D (χ2=10.45,9.12, P0.05). Compared with group S, the caspase-3/β-actin and apoptosis rate of group E were significantly higher (F=4.98, 5.17, P0.05). The caspase-3/β-actin and apoptosis rate of group D were significantly lower than group E (F=4.16, 4.98, P0.05). At 1h, 2h, 3h, 4h and 6h after modeling, the IL-6 and IL-10 in group E and group D were significantly higher than group S(t=6.85, 5.94,5.21,4.88,5.17,6.13,5.31,5.03,4.93,4.82,3.98,4.75,5.15,5.87,7.11,6.13,5.31,5.03,4.93,4.82,P<0.05). At 1h, 2h, 3h, 4h and 6h after modeling, the IL-6 and IL-10 in group D were significantly lower than group E (t=4.95,4.31,5.02,5.17,6.02,3.86,4.97,5.12,5.32,5.76,P<0.05). Conclusion Dexmedetomidine can regulate the immune response of rats with sepsis, and reduce the serum level of IL-6, IL-10 and the mortality.%目的:探讨右美托咪定对脓毒血症大鼠生存率和血清白细胞介素(IL)-6、IL-10的影响。方法将30只健康的雄性Wistar大鼠随机分为三组:0.9%氯化钠注射液组(S组)10只、内毒素组(E组)10只和右美托咪定治疗组(D组)10只。比较三组大鼠的生存率、血清IL-6IL-10水平及淋巴细胞凋亡率。结果经过6 h后,S组大鼠生存率为100%,E组大鼠生存率为30.00%,D组大鼠生存率为90.00%。 E组大鼠的生存率明显低于S组和D组,差

  2. 社区获得性肺炎患者血清及支气管肺泡灌洗液中IL-6、IL-8和IL-10水平变化及其临床意义%The levels of IL-6,IL-8 and IL-10 in serum and bronchoalveolar lavage fluid in patients with community-acquired pneumonia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    丁静; 魏希强; 孙伟

    2015-01-01

    目的::探讨社区获得性肺炎( CAP)患者血清和支气管肺泡灌洗液( BALF)中炎症因子白细胞介素( IL)-6、IL-8和IL-10水平的变化及其临床意义。方法:选取CAP患者50例( CAP组),入院第1天进行临床肺部感染评分,0.05);而CAP组血清中IL-8水平在入院第30天仍保持较高水平,显著高于对照组(P0. 05). The level of IL-8 in serum of CAP patients remained at a high level on day 30 of admission,which was significantly higher than that in control group(P <0. 01). Conclusions:The IL-6,IL-8 and IL-10 were involved in the pathogenesis of community-acquired pneumonia. The levels of IL-6 and IL-10 in serum and levels of IL-6,IL-8 and IL-10 in BALF can reflect the severity of pulmonary infection. The detection of IL-6,IL-8 and IL-10 in serum has certain clinical value in the early diagnosis of CAP.

  3. Memory B cells from older people express normal levels of cyclooxygenase-2 and produce higher levels of IL-6 and IL-10 upon in vitro activation.

    Science.gov (United States)

    Bancos, Simona; Phipps, Richard P

    2010-01-01

    Worldwide the elderly population is increasing. The elderly show deficiencies in immune function. B lymphocytes are essential elements of the immune system responsible for antibody production. This laboratory previously showed that activated human B cells isolated from young adults express cyclooxygenase-2 (Cox-2) and that Cox-2 is essential for optimal antibody responses. Recent data suggests that Cox-2 expression decreases with age in mouse bone tissue. There is no information regarding Cox-2 expression in B cells from older human subjects. We investigated the expression and activity of Cox-2 in naïve and memory B cells from older people. We show that B cells from older subjects show similar Cox-2 protein expression and activity, antibody production and proliferation compared to younger people. However, we found that activated memory B cells from older people produce higher levels of IL-6 and IL-10 compared to young adults. Therefore, the dysregulated cytokine production could contribute to immune senescence in the elderly.

  4. Human intestinal mucosa-associated Lactobacillus and Bifidobacterium strains with probiotic properties modulate IL-10, IL-6 and IL-12 gene expression in THP-1 cells.

    Science.gov (United States)

    Čitar, M; Hacin, B; Tompa, G; Štempelj, M; Rogelj, I; Dolinšek, J; Narat, M; Matijašić, B Bogovič

    2015-01-01

    Lactobacilli and bifidobacteria are considered one of the permanent genera of the physiological human intestinal microbiota and represent an enormous pool of potential probiotic candidates. Approximately 450 isolates of presumptive Lactobacillus or Bifidobacterium strains were obtained from bioptic samples of colonic and ileal mucosa from 15 adolescents aged 12 to 18 years. On the basis of randomly amplified polymorphic DNA (RAPD)-PCR analysis, 20 strains were selected for further taxonomic classification and characterisation, as well as assessment of probiotic properties and safety. Importantly, selected strains showed the capability of colonising different parts of the intestine. The most frequently isolated species was Lactobacillus paracasei followed by Lactobacillus fermentum. The majority of isolates were susceptible to antimicrobials of human and veterinary importance, however, tetracycline and/or erythromycin resistance was observed in Lactobacillus plantarum and L. fermentum strains. Thirteen strains were able to ferment more than 19 different carbon sources and three out of five tested strains exerted antagonistic activity against several different indicator strains. Two Lactobacillus isolates (L. paracasei L350 and L. fermentum L930 bb) and one Bifidobacterium isolate (Bifidobacterium animalis subsp. animalis IM386) fulfilled in vitro selection criteria for probiotic strains and exhibited strong downregulation of pro-inflammatory cytokines IL-6 and IL-12 and upregulation of anti-inflammatory IL-10. The selected strains represent suitable candidates for further studies regarding their positive influence on host health and could play an important role in ameliorating the symptoms of inflammatory bowel diseases.

  5. 右美托咪定对单肺通气患者血清TNF-ɑ、IL-6IL-10变化的影响%Effects of dexmedetomidine on perioperative serum TNF-ɑ, IL-6 and IL-10 levels in patients undergoing general anesthesia with one-lung ventilation

    Institute of Scientific and Technical Information of China (English)

    罗颖; 孙建良; 吴艳辉; 徐丽慧; 丁卫华

    2014-01-01

    目的:观察右美托咪定对单肺通气患者血清TNF-ɑ、IL-6IL-10变化的影响。方法选择择期全麻单肺通气下行开胸手术患者48例,采用随机数字表法分为右美托咪定组(D组)和对照组(C组),各24例。D组麻醉诱导前10 min经静脉输注右美托咪定1滋g/kg,随后以0.5滋g/(kg·h)的速率输注至术毕前30min。C组给予等量0.9%氯化钠溶液。于麻醉诱导前(T0)、单肺通气即刻(T1)、单肺通气30min(T2)、单肺通气90min(T3)、双肺通气后30 min(T4)和术后120min(T5)时间点采用酶联免疫吸附法测定血清TNF-ɑ、IL-6IL-10浓度,同时观察HR、MAP、SpO2的变化。结果两组患者各时点HR、MAP、SpO2差异均无统计学意义(均P>0.05)。与T0时比较,两组患者T2~T5时血浆TNF- a和IL-6浓度升高(P<0.05),与 C组比较,D组T2~T5时血浆TNF- a和IL-6浓度降低(P<0.05)。与T0时比较,两组患者T3~T5时血浆IL-10浓度升高(P<0.05),两组IL-10浓度的差异无统计学意义(P>0.05)。结论围手术期静脉持续输注右美托咪啶可降低炎性因子TNF-ɑ和IL-6的释放,明显减轻单肺通气患者围术期的炎性反应。%Objective To investigate the effects of dexmedetomidine on perioperative serum TNF- ɑ, IL- 6 and IL- 10 levels in patients undergoing general anesthesia with one lung ventilation (OLV). Methods Forty- eight patients who scheduled for thoracic surgery under general anesthesia with one lung ventilation were randomly divided into two groups (n=24 in each group):patients in group D were infused with dexmedetomidine 1μg/kg in 10min before anesthesia induction, and then infused at a rate of 0.5μg/ (kg·h) until 30 min before the end of operation;patients in group C received the equal volume of normal saline. Blood samples were col ected before induction of anesthesia(T0), at beginning of OLV(T1), 30min (T2) and 90min (T3) after OLV

  6. The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages

    Directory of Open Access Journals (Sweden)

    Blanco-Favela Francisco

    2010-10-01

    Full Text Available Abstract Atherosclerosis is considered a chronic inflammatory disease in which monocytes and macrophages are critical. These cells express CD14, toll-like receptor (TLR 2, and TLR4 on their surfaces, are activated by minimally modified low-density lipoprotein (mmLDL and are capable of secreting pro-inflammatory cytokines. The aim of this research was thus to demonstrate that the activation of CD14, TLR2, and TLR4 by mmLDL induces the secretion of cytokines. Methods Human monocytes and macrophages were incubated with monoclonal antibodies specific for CD14, TLR4, and TLR2 prior to stimulation with mmLDL. Cytokine secretion was then compared to that observed upon mmLDL stimulation in untreated cells. Results Stimulation with mmLDL induced the secretion of pro-inflammatory cytokines. Blocking CD14 in monocytes inhibited secretion of interleukin (IL-1β (72%, IL-6 (58% and IL-10 (63%, and blocking TLR4 inhibited secretion of IL-1β by 67%, IL-6 by 63% and IL-10 by 60%. Blocking both receptors inhibited secretion of IL-1β by 73%, IL-6 by 69% and IL-10 by 63%. Furthermore, blocking TLR2 inhibited secretion of IL-1β by 65%, IL-6 by 62% and IL-10 by 75%. In macrophages, we found similar results: blocking CD14 inhibited secretion of IL-1β by 59%, IL-6 by 52% and IL-10 by 65%; blocking TLR4 inhibited secretion of IL-1β by 53%, IL-6 by 63% and IL-10 by 61%; and blocking both receptors inhibited secretion of IL-1β by 69%, IL-6 by 67% and IL-10 by 65%. Blocking TLR2 in macrophages inhibited secretion of IL-1β by 57%, IL-6 by 40% and IL-10 by 72%. Conclusion Our study demonstrates that CD14, TLR4, and TLR2 participate in the immune response against mmLDL by inducing the production of pro-inflammatory cytokines in both monocytes and macrophages. These findings suggest that the activation of these receptors by mmLDL contributes to the inflammatory process of atherosclerosis.

  7. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine response in a Danish Cohort

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Albrechtsen, Anders; Thørner, Lise Wegner

    2013-01-01

    Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production....

  8. THE INFLUENCE OF POLYMORPHISM IN THE INFLAMMATORY GENES IL-1, ß IL-6, IL-10, PPAR?2 AND COX-2 IN PATIENTS WITH MULTIPLE MYELOMA UNDERGOING AUTOLOGOUS BONE MARROW TRANSPLANTATION

    DEFF Research Database (Denmark)

    Vangsted, Annette; Klausen, Tobias W.; Gimsing, Peter

    2007-01-01

    longer survival as compared to the homozygous wild type allele TT carriers (relative risk=2.1; p=0.008). There was no statistically significant difference between men and woman. The polymorphism in IL-6 G-174C, IL-10 C592A, PPAR?2 Pro12 Ala, COX-2 A-1195G, and COX-2 T8473C did not influence overall...

  9. Effects of Traditional Chinese Medicine Qingre Lishi Yin on Expressions of IL-6mRNA and IL-8mRNA and IL-10mRNA and Secretion of IL-8 and IL-10 in HaCaT Cells%中药清热利湿饮对HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA及分泌IL-8、IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    范玉; 杜锡贤; 张春红

    2014-01-01

    目的:揭示中药清热利湿饮对人永生化角质形成细胞HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA和分泌IL-8、IL-10的作用机制.方法:以HaCaT细胞为研究对象,分别采用RT-PCR技术及ELISA方法观察中药清热利湿饮提取液对经TNF-α诱导活化的HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA和分泌IL-8、IL-10的影响.结果:清热利湿饮对经TNF-α诱导活化的HaCaT细胞IL-6mRNA和IL-8mRNA的表达有下调作用,在药物浓度为10g/L和12.5g/L时,HaCaT细胞IL-10mRNA的表达量增强较为明显,与TNF-α诱导活化组相比,有显著性差异(P<0.05或P<0.01).清热利湿饮对经TNF-α诱导活化的HaCaT细胞IL-8的分泌有不同程度的抑制作用,但对IL-10的影响不明显.结论:清热利湿饮可下调IL-6mRNA、IL-8mRNA的表达,上调IL-10mRNA的表达,且此作用随药物浓度的升高而增强;同时可降低细胞IL-8的分泌,但对IL-10的分泌无明显的作用.

  10. 慢性阻塞性肺疾病患者呼出气冷凝液中NO2-、LTB4、PGE2、IL-6IL-10水平的研究%Levels of NO2-, LTB4, PGE2, IL-6, IL-10 in exhaled breath condensate with acute exacerbation chronic obstructive pulmonary disease patients

    Institute of Scientific and Technical Information of China (English)

    黄平; 聂莉; 杜秀芳; 钟春; 宋冰; 陈济明; 周蓓

    2012-01-01

    目的 探讨慢性阻塞性肺疾病(COPD)患者呼出气冷凝液(EBC)中亚硝酸盐(NO2-)、白三烯B4(LTB4)、前列腺素E2(PGE2)、白介素6(IL-6)和IL-10的水平与气道炎症及肺功能的关系.方法 收集20例COPD患者和20名健康体检者,测定肺通气功能,收集EBC,用比色法测定EBC中NO2-水平,用ELISA法测定EBC中LTB4、PGE2、IL-6IL-10的水平.结果 ①COPD组EBC中NO2-和LTB4的水平分别为(2.029±1.992) μmol/L、(0.400 ±0.235)μmol/L,均显著高于健康对照组(0.400±0.235)μmol/L,(9.742±2.348) ng/L,差异有统计学意义(P值均<0.05);EBC中PGE2、IL-6IL-10的水平在两组间比较,差异均无统计学意义(P>0.05);COPD组EBC中NO2-、LTB4、PGE2、IL-6IL-10的水平与FEV/FVC和FEV%预计值无相关性(P>0.05).结论 COPD患者EBC中NO2-、LTB4与气道炎症及氧化应激有关系,PGE2、IL-6IL-10与气道炎症的关系需进一步研究,这些细胞因子与肺功能无相关性.%Objective To investigate the relationship between NO2-,LTB4,PGE2,IL-6 and IL-10levels in exhaled breath condensate (EBC) and airway inflammation as well as pulmonary function from COPD patients.Methods Twenty cases of COPD and twenty healthy control were enrolled.ALL subjects detected FEV1/FVC and FEV1% predict.EBC were collected using EcoScreen system.The NO2-levei in EBC was determined by the spectrophotometry.The levels of LTB4,PGE2,IL-6 and IL-10in EBC were measured by enzyme linked immuosorbent assay.Results The levels of NO2-and LTB4 in EBC of COPDgroup were significantly higher than that of the control group [(2.029 ± 1.992) μmol/L,(13.598±3.910)ng/L vs (0.400 ±0.235) μmol/L,(9.742 ±2.348) ng/L,respectively,all P <0.05].There were no signficant difference of PGE2,IL-6 and IL-10 levels in EBC both groups (all P >0.05).There were no correlation between NO2-,LTB4,PGE2,IL-6,IL-10 in EBC with FEV1/FVC and FEV1% predict (P >0.05).Conclusions The COPD patients NO2-and LTB4 levels in EBC

  11. 胸痹心痛与血清IL-6、IL-1O、IL-18水平关系的研究%Investigation on the Relationship between Levels of IL-6,IL-10,IL-18 in Serum and the Mechanism of Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    高建苑; 肖涛; 孙静

    2003-01-01

    目的研究胸痹心痛(冠心病心绞痛)发病与血清IL-6IL-10、IL-18水平变化的关系.方法观察胸痹心痛患者血清IL-6IL-10、IL-18的水平并与健康人对比.结果与稳定型心绞痛患者血清IL-10水平相比,不稳定型心绞痛患者血清IL-10水平较低,而IL-6水平较高;胸痹心痛患者IL-18水平均高于对照组.结论血清IL-6IL-10、IL-18水平的变化与胸痹心痛的发病密切相关.

  12. Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

    Science.gov (United States)

    Bustinduy, Amaya L; Sutherland, Laura J; Chang-Cojulun, Alicia; Malhotra, Indu; DuVall, Adam S; Fairley, Jessica K; Mungai, Peter L; Muchiri, Eric M; Mutuku, Francis M; Kitron, Uriel; King, Charles H

    2015-05-01

    In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for

  13. 危重病患者血清TNF—α、IL-1β、IL-6IL-10水平与APACHE II评分关系的临床意义

    Institute of Scientific and Technical Information of China (English)

    张永和

    2006-01-01

    目的观察危重病患者血清中细胞因子TNF-α、IL—1β、IL-6IL-10水平变化和进行急性生理学与慢性健康状况Ⅱ(APACHE11)评分的相关性。方法35按APACHEⅡ评分分值分为〈15分组(A组),15—20分组(B组)和〉20分组(C组),同时设立对照组。采用放免法和酶联免疫吸附法分别测定,血清TNF-α、IL—1β、IL-6IL-10的浓度。结果患者血清TNF-α、IL—1β、IL-6IL-10水平A、B和C三组均显著升高(P均〈0.01);APACHEⅡ分值越高,TNF-α、IL-1β、IL-6IL-10水平升高越显著。结论危重患者TNF-α、IL—1β、IL-6和IL—10水平血清含量与病情轻重程度呈明显正相关,APACHEⅡ评分系统对危重病患者进行评分有助于评定患者病情和预测死亡危险性。

  14. 有氧运动对酒精性肝损伤小鼠ALT、AST、IL-10IL-6等的影响%Effects of Aerobic Exercise on ALT, AST, IL-10 and IL-6 in Mice with Alcoholic Injury of Liver

    Institute of Scientific and Technical Information of China (English)

    蔡文丽; 张慧; 唐选; 牛英鹏

    2013-01-01

    目的:建立小鼠酒精性肝损伤模型,探讨有氧运动对小鼠酒精性肝损伤后肝功能的影响以及血液白细胞介素-10(IL-10)、白细胞介素-6(IL-6)和总抗氧化能力(T-AOC)等的变化.方法:40只8周龄小鼠随机分为N组(对照组)、E组(运动组)、AL组(酒精灌胃组)和E+AL组(运动+酒精灌胃组),分别施加有氧运动、酒精灌胃干预.10周后处死取脾脏、肝脏和血清,分别检测IL-10、T-AOC、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷草转氨酶(ALT)、谷丙转氨酶(AST)和IL-6.结果:(1)血清ALT和AST含量,AL组和E+AL组非常显著高于N组(P<0.01),AL组高于E+AL组(P<0.05);(2)脾脏IL-10含量,AL和E+AL组明显高于N组,E组低于N组,E+AL组高于AL组;AL组和E+AL组血清IL-6含量高于N组(P<0.01),E+AL低于AL组(P<0.05);(3)肝脏T-AOC,AL组、E+AL组低于(P<0.01、P<0.05)、E组高于(P<0.05)N组,AL组低于E+AL组(P<0.05);肝脏SOD,与N组比较,AL组(P<0.05)、E+AL组降低、E组升高,E+AL组高于AL组(P<0.05),MDA含量,与N组相比,E组降低(P<0.05),AL组升高(P<0.01);E+AL组显著性低于AL组(P<0.05).结论:乙醇在肝脏内代谢过程中会引起机体免疫反应和炎症反应,同时导致肝脏的脂质过氧化损伤;适度的有氧运动干预可提高各实验对象抗氧化能力和抗炎能力,促进机体免疫稳定,减轻肝脏脂质过氧化损伤和炎症损伤,对酒精灌胃所致肝细胞损伤、炎症反应具有一定的缓解作用,提高机体免疫稳定能力,但并不能阻止酒精性肝损伤的发生.

  15. The Robust and Modulated Biomarker Network Elicited by the Plasmodium vivax Infection Is Mainly Mediated by the IL-6/IL-10 Axis and Is Associated with the Parasite Load

    Directory of Open Access Journals (Sweden)

    Allyson Guimarães da Costa

    2014-01-01

    Full Text Available Background. Recent studies have shown that the inflammatory process, including the biomarker production, and the intense activation of innate immune responses are greater in the malaria caused by Plasmodium vivax than other species. Here, we examined the levels of serum biomarkers and their interaction during acute malaria. Material and Methods. Blood samples were collected from P. vivax-infected patients at admission and from healthy donors. Levels of serum biomarkers were measured by Cytometric Bead Assay or ELISA. Results. P. vivax infection triggered the production of both inflammatory and regulatory biomarkers. Levels of IL-6, CXCL-8, IFN-γ, IL-5, and IL-10 were higher in P. vivax-infected patients than in healthy donors. On the other hand, malaria patients produced lower levels of TNF-α, IL-12p70, and IL-2 than healthy individuals. While the levels of IL-10 and IL-6 were found independent on the number of malaria episodes, higher levels of these cytokines were seen in patients with higher parasite load. Conclusion. A mixed pattern of proinflammatory and regulatory biomarkers is produced in P. vivax malaria. Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in malaria patients and that this interaction seems to be associated with the parasite load.

  16. 儿童溃疡性结肠炎血清IL-1、IL-6IL-10及TNF-α水平变化

    Institute of Scientific and Technical Information of China (English)

    张晓杰; 王莹

    2015-01-01

    目的 检测儿童溃疡性结肠炎(UC)血清白细胞介素(IL)-1、IL-6IL-10及肿瘤坏死因子-α(TNF-α)水平,探讨其与溃疡性结肠炎的临床意义,为临床诊断和治疗提供依据.方法 选择北华大学附属医院2012年1月~ 2013年12月儿童UC患者67例作为观察组,轻、中度病变患儿39例,重症患儿28例.活动期37例,缓解期30例.早选取同期健康查体儿童60例作为对照组.检测两组不同儿童及不同程度UC患儿、治疗前后血清IL-1、IL-6、IL-10及TNF-α浓度.结果 观察组患者IL-1、IL-6与TNF-α水平均高于对照组(P<0.05),观察组IL-10低于对照组(P<0.05);重度患者IL-1、IL-6与TNF-α水平均高于轻中度患者(P<0.05);重度患者IL-10水平低于轻中度患者(P<0.05);活动期患者IL-1、IL-6与TNF-α均高于缓解期(P<0.05),活动期患者IL-10水平低于缓解期(P<0.05);UC患者治疗后,IL-1、IL-6与TNF-α水平均低于治疗前(P<0.05),治疗后IL-10水平高于治疗前(P<0.05).结论 UC患者外周血中IL-1、IL-6与TNF-α显著升高,并随着疾病和活动程度的增高而升高,IL-10降低,治疗后IL-1、IL-6与TNF-α显著降低,IL-10升高,对于临床诊断、治疗儿童UC具有较好的指导意义.

  17. The dynamic monitor critically ill pneumonia patient blood and the bronchial tube pulmonary alveolus fill in the cleaning solution IL-6, IL-8, the IL-10 content and significance%动态监测重症肺炎患者血液和支气管肺泡灌洗液中 IL-6、IL-8、IL-10 的含量及其意义

    Institute of Scientific and Technical Information of China (English)

    李国保; 李沛

    2009-01-01

    Objective The dynamic monitor critically ill pneumonia patient blood and in the bronchial tube pulmonary alveolus syringe fluid IL-6, IL-8, the IL-10 density change, discusses its clinical significance. Methods Receives this courtyard ICU the critically ill pneumonia patient, the selected patient in the course the 1st day, CPIS grades >6 to divide into the CPIS high grouping, the CPIS grading ≤6 divides into CPIS the low grouping. In the course 1st, 4, 7 day of extraction circumference venous blood makes the cell factor determination as well as the bronchial tube pulmonary alveolus syringe fluid inspection. Results Regardless in the blood in BALF, CPIS high grouping's IL-6, the IL-8 level is lower than CPIS the grouping obvious markup, the difference has the remarkable significance (P<0.01), CPIS groups the IL-10 level to be lower than high the grouping group CPIS to be slightly high, but not yet reaches the remarkable difference;In blood and BALF IL-6, IL-8 level and CPIS grading present related (P<0.05), in blood and BALF IL-10 level and CPIS grading not obvious relevance.Conclusion The critically ill pneumonia patient blood and in the bronchial tube pulmonary alveolus syringe fluid IL-6, the IL-8 level may reflect that the lung infects the degree, IL-8, the IL-10 level and the change tendency may reflect the patient prognosis situation.%目的 动态监测重症肺炎患者血液和支气管肺泡灌洗液中 IL-6、IL-8、IL-10 的浓度变化,探讨其临床意义.方法 收住本院ICU的重症肺炎患者,入选患者在病程的第 1 天,CPIS 评分>6 分为 CPIS高分组,CPIS 评分≤6 分为 CPIS 低分组.在病程的第 1、4、7 天抽取外周静脉血做细胞因子测定以及支气管肺泡灌洗液检查.结果 无论在血液中还是在 BALF 中,CPIS 高分组的 IL-6、IL-8水平比 CPIS 低分组明显增高,差异有统计学意义(P<0.01),CPIS 高分组 IL-10 水平比 CPIS 低分组组稍高,但尚未达显著差异;血液和 BALF

  18. Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

    Science.gov (United States)

    Mokhtar, Galila M; El-Beblawy, Nagham M S; Adly, Amira A; Elbarbary, Nancy S; Kamal, Tarek M; Hasan, Esraa M

    2016-04-01

    To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.

  19. 重症肺炎支原体肺炎肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平观察

    Institute of Scientific and Technical Information of China (English)

    叶新明; 钱克俭

    2010-01-01

    目的检测重症肺炎支原体肺炎患者支气管肺泡灌洗液(bronchial tube pul monary alveolus syringe fluid,BALF)中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(In-terleukin-8,IL-8)白细胞介素-10(Interleukin-10,IL-10)浓度,探讨其临床意义。方法收住ICU的重症肺炎支原体肺炎患者36例,其CPIS评分〉6分为CPIS高分组共15例,CPIS评分〈6分为CPIS低分组共21例;正常对照组24例。取支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平。结果重症肺炎支原体肺炎无论CPIS高分组和CPIS低分组支气管肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平明显高于对照组,差异有统计学意义(P〈0.01),CPIS高分组TNF-α、IL-6、IL-8水平高于CPIS低分组,差异有统计学意义(P〈0.01),CPIS高分组IL-10水平稍高于CPIS低分组,差异无统计学意义(P〉0.05)。2组治疗后恢复期TNF-α、IL-6、IL-8、IL-10水平均明显下降(P〈0.01)。结论 TNF-α、IL-6、IL-8、IL-10在重症肺炎的发生发展中起重要作用,是重症肺炎支原体肺炎诊断的重要因素之一。利用支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平变化对临床诊断治疗及预后有一定的临床价值。

  20. 帕瑞昔布超前镇痛对烧伤患者术后疼痛及血清IL-6和IL-1O表达的影响%Preemptive analgesia and effects of parecoxib on IL-6 and IL-10 expressions in burned patients

    Institute of Scientific and Technical Information of China (English)

    华海峰; 邹俊; 张中军

    2012-01-01

    目的 探讨帕瑞昔布超前镇痛对术后镇痛及血清IL-6IL-10水平的影响.方法 36例烧伤患者随机均分为两组:A组术毕前50 min缓慢静注帕瑞昔布40 mg;B组不施行超前镇痛.术后不行自控镇痛,在患者主诉疼痛难忍时肌注哌替啶75 mg/次.记录术后4、8、12、24 h静息VAS疼痛评分,并用放射免疫分析方法测定血清IL-6IL-10浓度.结果 A组术后4、8、12h的VAS评分均显著低于B组(P<0.01),血清IL-6水平低于B组,而IL-10水平高于B组(P<0.05).结论 术毕前预用帕瑞昔布可明显减少烧伤术后疼痛和炎性反应.%Objective To study the preemptive analgesia and effects of parecoxib on IL-6 and IL-10 expressions in burned patients. Methods Thirty-six burned patients were equally randomized to two groups of A( injected parecoxib 40 rag at 30 min before the end of operation) and B( without parecoxib as the control). Intramuscular injection of pethidine 75 mg was performed after operation if necessary. Postoperative pain was scored by VAS at 4, 8, 12, and 24 h after operation and the expressions of serum IL-6 and IL-10 were detected by radioimmunoassay. Results At 4,8 and 12 h after operation, the VAS scores were significantly less in group A than those in group B(P<0. 01), serum IL-6 was lower,but IL-10 was higher,in group A than those in group B(P<0. 05). Conclusion Preemptive analgesia with parecoxib 40 mg can effectively attenuate postoperative pain and inflammatory cytokine response after surgery for bum.

  1. 血清TNF-α、IL-6、IL-8、IL-10和IL-13在小儿支原体肺炎诊治中的意义

    Institute of Scientific and Technical Information of China (English)

    邓连瑞

    2013-01-01

    目的:探讨血清中细胞因子TNF-α、IL-6、IL-8、IL-10和IL-13在小儿肺炎支原体肺炎发病中的临床意义。方法将90例MPP患儿(轻症52例、重症38例)按采血时间分为治疗前组及治疗后组,对照组85例,采用酶联免疫吸附法(ELISA)检测MPP患儿入院治疗前和抗炎治疗后血清中TNF-α、IL-6、IL-8、IL-10和IL-13浓度,并与对照组比较,进行统计学分析。结果 MPP治疗前组TNF-α、IL-6、IL-8,IL-13显著高于对照组血清浓度(P0.05),但IL-10治疗后组与对照组比较,浓度升高具有统计学意义(P<0.05);MPP患儿重型组比轻型组比较,TNF-α、IL-6、IL-8和IL-13浓度明显升高(P<0.01)。结论 MPP患儿治疗前组较治疗后组及对照组血清TNF-α、IL-6、IL-8和IL-13含量升高,提示在MPP 发病机制中起重要作用,并与病情相关;而IL-10在治疗后较治疗前浓度升高,提示与机体恢复期免疫反应相关。

  2. LL-37, HNP-1, and HBD2/3 modulate the secretion of cytokines TNF-α, IL-6, IFN-γ, IL-10 and MMP1 in human primary cell cultures.

    Science.gov (United States)

    Medina Santos, Carlos Erik; López Hurtado, Carmen Nathaly; Rivas Santiago, Bruno; Gonzalez-Amaro, Roberto; Cataño Cañizales, Yolanda Guadalupe; Martínez Fierro, Margarita de la Luz; Enciso-Moreno, José Antonio; García Hernández, Mariana Haydee

    2016-09-01

    The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine and MMP production in human polymorphonuclear cells, mononuclear cells and chondrocytes. The levels of cytokines in supernatants from mononuclear and polymorphonuclear cell cultures were measured with a cytometric bead array by flow cytometry. Likewise, the levels of metalloproteinase/MMP-1, 3, and 13 were measured in supernatants from chondrocyte cultures using an ELISA. The expression of RANKL on lymphocytes was analyzed by flow cytometry. We observed increased levels of TNF-α, IL-6 and IL-10 in mononuclear and polymorphonuclear cell cultures stimulated with HBD-2/3. We also observed increased levels of IFN-γ, IL-10, and IL-6 in mononuclear cell cultures stimulated with HNP-1, and increased IL-6 levels were observed in polymorphonuclear cell cultures exposed to HNP-1. We also found that the MMP-1 level increased in the chondrocyte cultures stimulated with HBD-3, whereas the MMP-1 level was decreased in cultures exposed to LL-37. The present report is the first study to determine that HNP-1and HBD2/3 promote the secretion of pro-inflammatory cytokines by polymorphonuclear and mononuclear cells and the secretion of MMP by chondrocytes, whereas LL-37 diminishes MMP1 secretion. Our results suggest that HBD-2/3 and HNP1 might play a pathological role in rheumatoid arthritis, while LL-37 might have a protective role.

  3. The Effects of Yerba Maté (Ilex Paraguariensis) consumption on IL-1, IL-6, TNF-α and IL-10 production by bone marrow cells in wistar rats fed a high-fat diet.

    Science.gov (United States)

    Carmo, Luciana Simão; Rogero, Marcelo Macedo; Cortez, Mayara; Yamada, Monica; Jacob, Patrícia Silva; Bastos, Deborah Helena Markowicz; Borelli, Primavera; Ambrósio Fock, Ricardo

    2013-01-01

    An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba maté (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL-1α, IL-6, TNF-α, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1α, IL-6, and TNF-α, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1α, IL-6, and TNF-α production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1α, IL-6, and TNF-α production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1α, IL-6, and TNF-α by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS.

  4. 大承气汤对ES大鼠血液中TNF-α、IL-1、IL-6IL-10、IL-13的影响

    Institute of Scientific and Technical Information of China (English)

    周晓红; 翟佳

    2004-01-01

    目的:研究大承气汤对内毒素休克大鼠血中TNF-α、IL-1、IL-6IL-10、IL-13浓度的影响,来探讨其抗ES的机制。方法:将大鼠随机分为NS对照组,与实验组等量的生理盐水(NS)注射及灌胃;LPS组,尾静脉注入LPS 8mg/kg b.w.;LPS+DD组,大承气汤灌胃30min后,尾静脉注入LPS(剂量同LPS组)。3h后取血留血浆备用。结果:LPS组动物血浆中TNF-α、IL-1、IL-6IL-10、IL-13的含量较NS对照组明显升高(P<0.05),IPS+大承气汤组动物血浆中TNF-α、IL-1、IL-6的含量较LPS组明显降低(P<0.05),IL-10、IL-13的含量明显升高(P<0.05)。结论:大承气汤可通过影响细胞因子网络来发挥抗KS的作用。

  5. Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort.

    Directory of Open Access Journals (Sweden)

    Margit Hørup Larsen

    Full Text Available Cytokine response plays a vital role in various human lipopolysaccharide (LPS infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF-α cytokine production.We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals.Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(-7. However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages.The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered.

  6. Structural characterization and immunomodulatory effects of polysaccharides from Phellinus linteus and Phellinus igniarius on the IL-6/IL-10 cytokine balance of the mouse macrophage cell lines (RAW 264.7).

    Science.gov (United States)

    Suabjakyong, Papawee; Nishimura, Kazuhiro; Toida, Toshihiko; Van Griensven, Leo J L D

    2015-08-01

    Phellinus linteus and igniarius (L.) Quel. have been used in traditional Asian medicine for over two centuries against a variety of diseases. Polysaccharides from their fruiting bodies show strong immunomodulatory activity. In this study we characterized the structure and composition of polysaccharides from Phellinus linteus and Phellinus igniarius by HPLC, GC-MS and NMR (1-H, 13-C, COSY, NOESY and TOCSY). The polysaccharides from P. linteus and P. igniarius mainly contained glucose with minor proportions of mannose, galactose, xylose, arabinose and rhamnose. Methylation analyses showed that the glycosidic linkages were mostly 1 → 3, 1 → 6 or 1 → 3,6. The two-dimensional COSY, NOESY and TOCSY confirmed that these polysaccharides have a main chain of →3)-β-D-Glcp-(1→ with →6)-β-D-Glcp-(1→ side chain. In vitro assays by RT-PCR and ELISA showed that (1 → 3; 1 → 6)-β-D-polysaccharides from P. linteus and P. igniarius decreased TNF-α in RAW 264.7 cells, suggesting an immuno-suppressive activity. Furthermore, these polysaccharides stimulated a high IL-10 response and induced strong suppression of transcription of IL-6. The results suggest that polysaccharides from P. linteus and P. igniarius could possibly find applications in restoring the IL-6/IL-10 balance, the disturbance of which is thought to be related to chronic inflammatory disease, obesity, diabetes type 2, and to mania and depression.

  7. Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4⁺ T cells from patients with GI malignancy.

    Science.gov (United States)

    Mundy-Bosse, Bethany L; Young, Gregory S; Bauer, Todd; Binkley, Elaine; Bloomston, Mark; Bill, Matthew A; Bekaii-Saab, Tanios; Carson, William E; Lesinski, Gregory B

    2011-09-01

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33(+)HLADR(-)CD11b(+)CD15(+) and CD33(+)HLADR(-/low)CD14(+) MDSC subsets were also elevated in patients versus normal donors (P normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33(+)HLADR(-)CD15(-) MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33(+)HLADR(-/low)CD14(+) subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  8. IL-10,IL-6IL-6受体基因多态性与皮肤黑素瘤易感性的关系%Relationships between Genetic Polymorphisms of Interleukin-10,Interleukin-6,Interleukin-6 Receptor and Patients' Susceptibility to Melanoma

    Institute of Scientific and Technical Information of China (English)

    钟桂书; 任培蓉; 史丙俊; 曾凡才; 黄忠奎; 熊霞

    2011-01-01

    目的 探讨白介素10(IL-10)、白介素6(IL-6)及其受体(IL-6R)基因多态性与黑素瘤易感性的关系.方法 收集30例黑素瘤患者和30例健康时照者的外周血样本进行基因型分析.对于IL-6IL-6R,选择11种单核苷酸多态性(SNPs),并且每种SNPs分为杂合子组、纯合子变异体组和野生型组进行分析.对于IL-10,选择-1082(G/A),-819(C/T)和-592(C/A)三个位点的SNPs进行基因型分析.结果 在IL-6R基因中发现有4种SNPs(rs6684439,rs4845618,rs4845622,rs8192284)的杂合子组与黑素瘤易感性增高有关(相应的OR及95% CI分别为:1.71,1.12-2.77;1.74,1.04-2.72; 1.65,1.05-2.71; 1.66,1.06-2.68).与对照组比较,病例组患者IL-10-1082 AA低表达基因型频率明显升高(40.00% vs 16.67%; P=0.045; OR = 3.33,95% CI 1.00~11.14),-1082 GA中表达基因型下降(46.67% vs 56.67% ;P>0.05),-1082 GG高表达基因型无明显差异(26.67% vs23.33%;P>0.05),结论与高表达水平IL-10相关的基因型与黑素瘤易感性无明显相关性,而低表达基因型则可能为危险因子,可能提高黑素瘤易感性;IL-6R可能与黑素瘤易感性增高有关.%Objective To investigate the relationships between genetic polymorphisms of interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-6 receptor (IL-6R) and patients' susceptibility to melanoma.Methods Peripheral blood samples were collected from 30 patients with melanoma ( melanoma group ) and 30 healthy controls (control group), and then were analyzed for genotype.For IL-6 and IL-6R, 11 kinds of single nucleotide polymorphisms (SNPs) were selected, and then each was divided into 3 subgroups: heterozygote group, homozygous variant group, and wild type group.For IL-10, the SNPs of -1082 (G/A), -819 (C/T), and -592 (C/ A) were selected to give genotype analyses.Results Heterozygote groups of 4 kinds of SNPs, which were rs6684439, rs4845618, rs4845622, and rs8192284, in IL-6R gene were discovered to be related to an increase of susceptibility

  9. Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance Níveis séricos de IL-6, IL-10 e TNF-α em pacientes com transtorno bipolar e esquizofrenia: diferenças no equilíbrio pró e antiinflamatório

    Directory of Open Access Journals (Sweden)

    Mauricio Kunz

    2011-01-01

    Full Text Available OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p OBJETIVO: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. MÉTODO: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia cronicamente estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos são não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. RESULTADOS: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001 e aos pacientes bipolares eutímicos (p < 0,0001. Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357. Os níveis de IL-10 foram menores nos controles quando comparados aos esquizofrenia (p = 0,001 ou aos bipolares (p = 0,004. Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos (p = 0,284. A separação por sexo não mostrou diferenças significativas e não houve correlação entre a dose de antipsicóticos e os níveis de citocinas em pacientes com esquizofrenia. DISCUSSÃO: Estes resultados evidenciam uma ativação imune

  10. Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance Níveis séricos de IL-6, IL-10 e TNF-α em pacientes com transtorno bipolar e esquizofrenia: diferenças no equilíbrio pró e antiinflamatório

    Directory of Open Access Journals (Sweden)

    Mauricio Kunz

    2011-09-01

    Full Text Available OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p OBJETIVO: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. MÉTODO: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia crônica estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos eram não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. RESULTADOS: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001 e aos pacientes bipolares eutímicos (p < 0,0001. Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357. Os níveis de IL-10 foram menores nos controles quando comparados aos pacientes com esquizofrenia (p = 0,001 ou aos bipolares (p = 0,004. Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos (p = 0,284. A separação por sexo não mostrou diferenças significativas e não houve correlação entre a dose de antipsicóticos e os níveis de citocinas em pacientes com esquizofrenia. DISCUSSÃO: Estes resultados evidenciam uma ativa

  11. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

    Directory of Open Access Journals (Sweden)

    Iona E. Maher

    2014-03-01

    Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

  12. TNF-alpha, TGF-beta, IL-10, IL-6, and INF-gamma alleles among African Americans and Cuban Americans. Report of the ASHI Minority Workshops: Part IV.

    Science.gov (United States)

    Delaney, Nancy L; Esquenazi, Violet; Lucas, Donna P; Zachary, Andrea A; Leffell, Mary S

    2004-12-01

    Point mutations or single nucleotide substitutions in the regulatory regions of cytokine genes may affect levels of cytokine expression and have been associated with acute and chronic rejection in organ transplantation, severity of graft-versus-host disease in hematopoietic stem cell transplants, and predisposition to autoimmune disorders. Because these cytokine variants have been studied primarily among Caucasians, we defined the alleles and frequencies of five cytokines among 691 unrelated, adult African Americans and 296 Cuban Americans in the American Society for Histocompatibility/National Institutes of Health Minority HLA Workshops. The genotypes of all cytokines, except for transforming growth factor (TGF)-beta among African Americans, were found to be in Hardy-Weinberg's equilibrium. Genotype frequencies among African American and Cuban American participants were compared with those of 75 North American Caucasian bone marrow donors and with published frequencies. Significant differences were observed in all comparisons except between Cuban and Caucasian Americans for alleles of interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. The most notable differences were in genotype frequencies of African Americans compared with those of the two other populations. The frequency of the IFN-gamma genotype A/A, which is associated with low expression, was significantly higher in African Americans than in Caucasian or Cuban Americans (0.66 vs 0.37 and 0.26, respectively; p < 0.0001 for both comparisons). The high-expression G/G genotype for IL-6 was more than twice as prevalent among African Americans as among Caucasians and 1.5 times more frequent than among Cuban Americans (respective frequencies: 0.85 vs 0.38 and 0.49; p < 0.0001 for both comparisons). In African Americans, the frequency of the high-expression genotype for IL-10, GCC/GCC, was approximately half that of the frequency in Cuban and Caucasian Americans (0.10 vs 0.19 and 0.23, respectively; p < 0

  13. 连续性血液净化对SIRS/sepsis合并ARF患者血清PCT、TNF-а、IL-6IL-10等的影响%Effect of continuous blood purification on the serum levels of PCT and cytokines of TNF-α,IL-6, IL-10 in patients with systemic inflammatory response syndrome or sepsis combined with acute renal failure

    Institute of Scientific and Technical Information of China (English)

    孙晨; 吴学敏; 魏鹍

    2010-01-01

    目的 探讨连续性静脉-静脉血液透析(CVVH)技术对系统性炎性反应综合征(SIRS)/脓毒症(sepsis)合并急性肾衰患者体内降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、IL-10等炎性因子的清除作用,同时观察连续性血液净化(CBP)对肾功能、血流动力学的治疗作用和预后的影响.方法 选择ICU行CVVH治疗的患者 18例,其中非感染SIRS 9例,感染SIRS(脓毒症)9例.于CVVH治疗前及治疗后2、6、12 h及CVVH停止后12 h,分别检测血清PCT、TNF-α、IL-6IL-10浓度;抽取静脉血检测血液电解质及肾功能;抽动脉血检测血气分析,记录pH值、动脉血氧分压、动脉血二氧化碳分压;于上述各时间点记录体温(T)、心率(HR)、呼吸(R)、平均动脉压(MAP)、中心静脉压(CVP).结果 sepsis组血清PCT的初始浓度明显高于SIRS组(P0.05); 18例患者CBP治疗后血清TNF-α水平在CBP后2、6、12 h时均显著低于CBP前(P0.05); CVVH后BUN、Scr、血清K+均下降(P<0.05),在停止CBP后12 h虽然略有所回升,但仍明显低于CVVH前(P<0.05).结论 CBP能清除SIRS/Sepsis合并ARF患者血清中多种炎性因子.其过程中血流动力学平稳,对SIRS/Sepsis合并ARF患者有良好的治疗作用.

  14. Effect of ultraviolet ray on expression of IL6 and IL10mRNA in peripheral blood monocytes of systemic lupus erythematosus cases%紫外线对SLE白介素-6和白介素-10mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐文英; 郭庆

    2012-01-01

    目的 探讨紫外线对系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)表达白介素-6(IL-6)、白介素-10(IL-10)mRNA的影响.方法 提取SLE患者及健康对照的PBMC,用不同剂量311nm窄谱中波紫外线(NB-UVB)照射,以实时荧光相对定量聚合酶链反应分析照射前后PBMC IL-6IL-10mRNA的相对表达.结果 SLE患者中狼疮肾炎(LN)患者PBMC高表达IL-6IL-10mRNA,与非狼疮肾炎(非LN)患者及正常人差异很大,分别是正常人的(105.44±112.94)倍和(1.82±3.41)倍、(28.41±21.14)倍和(1.17±1.43)倍,其中狼疮肾炎(LN)患者PBMC高表达IL-6IL-10 mRNA,且与临床中24h尿蛋白定量高度相关(r=0.82,0.87,P<0.05),而非狼疮肾炎系统性红斑狼疮患者与正常人相比,差异无统计学意义(t'=0.43,0.87,P>0.05);在紫外线照射后LN患者PBMC IL-6IL-10mRNA的表达有升高也有降低,升高组SLE疾病活动指数、抗SSA抗体阳性率以及光敏性发生率明显高于降低组.结论 紫外线可改变SLE患者PBMC表达IL-6IL-10mRNA,紫外线可能通过此途径影响SLE病情.%Objective To observe the impact of ultraviolet ray on the expression of IL-6, IL-10mRNA of peripheral blood monocytes (PBMC)from systemic lupus erythematosus (SLE). Cases. Methods PBMC were isolated from SLE patients and healthy controls .Then they were irradiated with 311 nm narrow band-ultraviolet ray (NB-UVB)in various dbsages.IL-6,IL-10mRNA expression was measured by real-time quantitative PCR. Results The expression of IL-6, IL-10mRNA in SLE patient was very different. IL-6,IL-10mRNA were highly expressed in PBMC from lupus nephritis (LN),and its expression was highly related with 24-hour urinary protein quantitative (r=0.82,0.87,P0.05). The expression of IL-6,IL-10mRNA in LN could increase or decrease after exposured to ultraviolet ray. But the anti-SSA antibody positive rate, systemic lupus erythematosus activity index (SLEDAI)and photosensitivity in exopression -elevated group

  15. Clinical Significance of Determination of Changes of Serum IL-6, IL-8, IL-10 and IL-18 Levels After Treatment in Patients with Chronic Renal Diseases%慢性肾病患者细胞因子测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    刘从江; 李芬; 张磊; 刘剑华

    2008-01-01

    目的:探讨了慢性肾病患者血清IL-6、IL-8、IL-10和IL-18水平的变化及意义.方法:分别应用放射免疫分析和酶联法对32例慢性肾病患者进行了血清IL-6、IL-8、IL-10和IL-18测定,并与35名正常健康人作比较.结果:慢性肾病患者血清IL-6、IL-8、IL-10和IL-18水平显著地高于正常人组(P<0.01),经治疗6个月后与正常人组比较仍有差异(P<0.05).结论:检测慢性肾病患者血清IL-6、IL-8、IL-10和IL-18水平的变化对疾病的预后观察具有重要的临床价值.

  16. 氧化苦参碱对急性坏死性胰腺炎大鼠血清和胰腺组织中炎性介质的影响%The role of oxymatrine on serum and pancreas tissue changes of TNF-α,IL-1β, IL-6 and IL-10 in rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    李海军; 庞作良; 毛拉艾沙·买买提; 孙晓宏; 王晓文

    2007-01-01

    目的:探讨氧化苦参碱(OMT)对急性坏死性胰腺炎(ANP)大鼠血清和胰腺组织中TNF-α、IL-1β、IL-6IL-10含量的影响及其意义.方法:选择标准Wistar大鼠120只,随机分为3组:假手术组(SO组)、ANP组和ANP+OMT组, 以牛磺胆酸钠复制急性坏死性胰腺炎大鼠模型.OMT用药方法为胰管内给予牛磺胆酸钠后15 min腹腔内注射给药50mg·kg-1·h-1,共3次.动态观察同组不同时间(4、8、12、16 h)及不同组同时间的血清和胰腺组织中内毒素(ET)、TNF-α、IL-1β、IL-6IL-10含量变化,同时观察各组大鼠胰腺组织的病理变化、大鼠24 h病死率及平均生存时间.结果: ANP组和ANP+OMT组在4、8、12和16 h的血清和胰腺组织中ET、TNF-α、IL-1β、IL-6IL-10 (ANP组IL-10除16 h外)均显著高于SO组(P<0.01~0.05), 且ANP组和ANP+OMT组ET、TNF-α、IL-1β和IL-6随病程进展而升高(P<0.05);ANP组 IL-10水平随病程进展降低(P<0.05),ANP+OMT组IL-10水平随病程进展增高(P<0.05).在相同时段除ET在ANP组和ANP+OMT组差异无统计学意义外(P>0.05),ANP组TNF-α、IL-1β和IL-6水平显著高于ANP+OMT组(P<0.01),而ANP+OMP组IL-10水平(除4 h组外)显著高于ANP组(P<0.01~0.05).ANP组和ANP+OMT组大鼠胰腺组织的病理变化无明显差异,但ANP+OMT组大鼠24 h病死率显著低于ANP组(P<0.05),平均生存时间较ANP组显著延长(P<0.05).结论: OMT可减少促炎细胞因子TNF-α、IL-1β和IL-6 的产生,上调抗炎细胞因子IL-10的负调控作用,有助于减轻ANP时炎性细胞因子瀑布样级联反应,降低大鼠24 h病死率,延长平均生存时间.

  17. Pregnancy Specific Glycoprotein 17 Binds to the Extracellular Loop 2 of Its Receptor, CD9, and Induces the Secretion of IL-10, IL-6, PGE2, and TGFBeta1 in Murine Macrophages

    Science.gov (United States)

    2004-01-01

    deficiency of placental IL-10 in preeclampsia . J Immunol, 1999. 163(6): p. 3491-5. 53. Raghupathy, R., et al., Maternal Th1- and Th2-type reactivity to...such as progesterone regulate the immune response at locations far from its original site of production but its use for the management of autoimmune...M.S. Wilson, Value of Schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein-A (PAPP-A) in the clinical management of threatened

  18. 川崎病患儿血清白细胞介素-6、-10、-1水平变化及意义%Changes of serum IL-6, IL-10 and IL-1 in patients with Kawasaki disease and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    吕慧; 贠国俊

    2012-01-01

    Objective To observe the serum levels of IL-6,IL-10 and IL-1 in children with Kawasaki disease and its clinical significance.Methods 38 childrey with of Kawasaki disease were selected as observction group,then selected 38 cases of normal children as control group.Serum IL-6,IL-10 and IL-1 levels were observed two groups.Results Observation group IL-6,IL-10 and IL-1 levels were higher(t =10.3877,15.1010,15.1243,all P<0.05),acute phase of observation group IL-6,IL-10,IL-1,etc.levels were significantly higher than the sub-acute phase patients ( t =9.7594,11.6486,11.6622,all P < 0.05 ) and control group ( t =11.7032,11.7718,11.8267,all P <0.05 ).48h apoptosis rate in the control group( 2.8 ± 0.8 )% was significantly lower than in children with Kawasaki disease(38.3 ±7.9)% (t =38.59,P <0.01 ).Platelets increased[ (464.0 ± 110.2) × 109/L] of the IL-1 level in children with Kawasaki disease(663 ±94)ng/L was significantly higher than those without elevated platelet [ (307.0 ±104.9) × 109 /L ] of children( 492 ± 92 ) ng/L ( t =13.1044,P < 0.05 ).Conclusion Thedetection of serum IL-6,IL-10 and IL-1 levels may aid clinical diagnosis of the condition of children with Kawasaki disease,complications and treatment,have important clinical significance.%目的 观察川崎病患儿血清白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-1(IL-1)水平变化及其临床意义.方法 选取38例川崎病患儿(观察组)和38例健康儿童(对照组)血清IL-6IL-10和IL-1水平,观察两组差异及对治疗效果的影响.结果 观察组IL-6IL-10和IL-1水平均高于对照组(t=10.3877、15.1010、15.1243,均P<0.05),观察组急性期IL-6IL-10、IL-1等水平明显高于亚急性期患儿(t=9.7594、11.6486、11.6622,均P<0.05)及对照组(t=11.7032、11.7718、11.8267,均P<0.05).对照组48 h内细胞凋亡率为(2.8±0.8)%,明显低于川崎病患儿的(38.3±7.9)%(t=38.59,P<0.01).血小板升高[(464.0±110.2)×109/L

  19. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

    Science.gov (United States)

    Tsilidis, Konstantinos K.; Helzlsouer, Kathy J.; Smith, Michael W.; Grinberg, Victoriya; Hoffman-Bolton, Judith; Clipp, Sandra L.; Visvanathan, Kala

    2011-01-01

    Objective and methods The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53–1.18) or two (OR, 0.58; 95% CI, 0.35–0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (ptrend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. PMID:19760027

  20. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass

    DEFF Research Database (Denmark)

    Kirchner, Henriette; Nylen, Carolina; Laber, Samantha;

    2014-01-01

    Background Early benefits of Roux-en Y gastric bypass (RYGB) are partly mediated by the caloric restriction that patients undergo before and acutely after the procedure. Altered DNA methylation occurs in metabolic diseases including obesity, as well as in skeletal, muscle eight months after RYGB...

  1. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II.

    Science.gov (United States)

    Wang, Ming-Hsi; Helzlsouer, Kathy J; Smith, Michael W; Hoffman-Bolton, Judith A; Clipp, Sandra L; Grinberg, Viktoriya; De Marzo, Angelo M; Isaacs, William B; Drake, Charles G; Shugart, Yin Yao; Platz, Elizabeth A

    2009-06-01

    Chronic intra-prostatic inflammation and obesity are thought to influence prostate carcinogenesis. Thus, variants in genes in these pathways could be associated with prostate cancer risk. We genotyped 17 common single nucleotide polymorphisms (SNPs) in RNASEL, TLR4, IL1B, IL6, IL8, IL10, TNF, CRP, ADIPOQ, LEP, PPARG, and TCF7L2 in 258 white prostate cancer cases and 258 matched controls nested in CLUE II. Single-locus analyses were conducted using conditional logistic regression. TagSNPs were selected in IL10, CRP, and TLR4 and haplotype analyses were done. The A allele of IL10 -1082G>A (rs1800896), known to result in lower levels of this anti-inflammatory cytokine, was positively associated with risk (AG vs. GG, OR = 1.69, 95% CI: 1.10-2.60; AA vs. GG, OR = 1.81, 95% CI: 1.11-2.96; P (trend) = 0.02). Associations of IL10 haplotypes with prostate cancer were explained by high linkage disequilibrium between two tagSNPs (rs1800890 and rs3024496) and -1082G>A. A TLR4 candidate SNP (rs4986790; AG/GG vs. AA, OR = 0.60, 95% CI: 0.33-1.08; P(trend) = 0.09), known to have decreased expression and be associated with lower circulating levels of inflammatory mediators, and tagSNP (rs10116253; CC vs. TT, OR = 3.05, 95% CI: 1.11-8.41), but not haplotypes, were associated with risk. None of the other candidate SNPs or haplotypes was statistically significantly associated with risk. Our prospective study suggests that genetic variation in IL10 and possibly TLR4 is associated with prostate cancer risk. Although none of the SNPs in the obesity genes tested was associated, this does not rule out a complex role of obesity and its metabolic consequences in prostate cancer etiology. . (c) 2009 Wiley-Liss, Inc.

  2. Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development.

    Science.gov (United States)

    Dill, Alisa; Letra, Ariadne; Chaves de Souza, Letícia; Yadlapati, Mamatha; Biguetti, Claudia Cristina; Garlet, Gustavo Pompermaier; Vieira, Alexandre R; Silva, Renato Menezes

    2015-02-01

    It has been proposed that individual genetic predisposition may contribute to persistent apical periodontitis. Cytokines are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. We hypothesized that polymorphisms in cytokine genes may contribute to an individual's increased susceptibility to apical tissue destruction in response to deep carious lesions. Subjects with deep carious lesions with or without periapical lesions (≥3 mm) were recruited at the University of Pittsburgh, Pittsburgh, PA, and the University of Texas at Houston, Houston, TX. Genomic DNA samples of 316 patients were sorted into 2 groups: 136 cases with deep carious lesions and periapical lesions (cases) and 180 cases with deep carious lesions but no periapical lesions (controls). Nine single-nucleotide polymorphisms in IL1B, IL6, TNF, RANK, RANKL, and OPG genes were selected for genotyping. Genotypes were generated by end point analysis using TaqMan chemistry (Invitrogen, Carlsbad, CA) in a real-time polymerase chain reaction instrument. Allele and genotype frequencies were compared among cases and controls using the PLINK program (http://pngu.mgh.harvard.edu/purcell/plink/). Ninety-three human periapical granulomas and 24 healthy periodontal ligament tissues collected postoperatively were used for messenger RNA expression analyses of IL1B. A single-nucleotide polymorphism in IL1B (rs1143643) showed allelic (P = .02) and genotypic (P = .004) association with cases of deep caries and periapical lesions. We also observed altered transmission of IL1B marker haplotypes (P = .02) in these individuals. IL1B was highly expressed in granulomas (P carious lesions. Future studies could help predict host susceptibility to developing periapical lesions. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not associated with cerebral malaria in Thailand

    OpenAIRE

    Tangpukdee Noppadon; Hananantachai Hathairad; Patarapotikul Jintana; Doi Akihiro; Naka Izumi; Ohashi Jun; Looareesuwan Sornchai; Tokunaga Katsushi

    2005-01-01

    Abstract Background IL-1β and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T. Methods To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 c...

  4. Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy.

    Science.gov (United States)

    Chen, Fang; Teachey, David T; Pequignot, Edward; Frey, Noelle; Porter, David; Maude, Shannon L; Grupp, Stephan A; June, Carl H; Melenhorst, Jan J; Lacey, Simon F

    2016-07-01

    T cells expressing a CD19-specific chimeric antigen receptor (CAR19) are demonstrating remarkable efficacy in hematologic malignancies. Treatment is often associated with life-threatening cytokine release syndrome (CRS) which can be effectively treated with cytokine blockade using the antibodies, Siltuximab or Tocilizumab respectively targeting IL-6 or the IL-6 receptor. As IL-6 blockade is moving into the clinic for the treatment of CRS as well as IL-6-driven rheumatologic and malignant diseases, clinicians are utilizing serum cytokine panels more frequently to assess the effects of IL-6 inhibitors. It is paramount to ascertain whether levels obtained are accurate, especially as certain drugs may, in theory, affect quantification. We report the comparative quantification of IL-6 and sIL-6R using Luminex-based immunoassay kits from two vendors. Our results indicate good agreement of the commercial immunoassays in measurement of IL-6 but disagreement in quantitation of sIL-6R. We found that both Siltuximab and Tocilizumab can interfere with the measurement of their respective ligands using reagents from one vendor but not the second. This has significant implications for the analysis of IL-6 and sIL-6R pharmacokinetics analysis in Siltuximab or Tocilizumab-treated patients. We found that high levels of IL-6 can falsely reduce the measured levels of sIL-6R and high levels of sIL-6R can reduce levels of IL-6 when measured with some commercial assays. These data demonstrate the importance of assessing the impact of cytokine-blocking agents on accuracy of clinical biomarker assays in other diseases, as drugs targeting TNF-alpha, IL1B, and IL5 are being used more frequently in a large number of diseases.

  5. IL-1B rs16944 polymorphism is related to septic shock and death.

    Science.gov (United States)

    Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

    2017-01-01

    IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  6. Interleukins IL-6, IL-8, IL-10, IL-12 and periimplant disease. An update

    National Research Council Canada - National Science Library

    Candel-Martí, Maria-Eugenia; Flichy-Fernández, Antonio-Juan; Alegre-Domingo, Teresa; Ata-Ali, Javier; Peñarrocha-Diago, Maria A

    2011-01-01

    ... (IL-12)) as markers of periimplant disease (mucositis and periimplantitis). An increase in the levels of these cytokines in dental implant crevicular fluid may give rise to a lack of osteointegration, bone loss or implant failure...

  7. Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor.

    Science.gov (United States)

    Van Wagoner, N J; Oh, J W; Repovic, P; Benveniste, E N

    1999-07-01

    In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-alpha or IL-1beta on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-alpha or IL-1beta plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-alpha- or IL-1beta-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-alpha or IL-1beta plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-alpha for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-alpha and IL-1beta.

  8. Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

    DEFF Research Database (Denmark)

    Stegger, Jakob Gerhard; Schmidt, Erik Berg; Tjonneland, Anne;

    2012-01-01

    Background: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary...... and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire...... IL1B haplotypes and risk factors, respectively. Conclusions/Significance: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years....

  9. The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study

    DEFF Research Database (Denmark)

    Andersen, V.; Ernst, A.; Christensen, J.

    2010-01-01

    Background: Crohns disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (HO-1/HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas...... the pro-inflammatory interleukin 1 beta (IL-1 beta/IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1 beta, IL-10, and HO-1 genes, together with smoking...

  10. Knocking out IL-6 by vaccination

    DEFF Research Database (Denmark)

    Galle, Pia; Hougs, Lotte; Barington, Torben

    2004-01-01

    Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination...

  11. IL-6 Compared to Young Mice

    Directory of Open Access Journals (Sweden)

    Jihyun Park

    2014-01-01

    Full Text Available Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly.

  12. IL-6 and mouse oocyte spindle.

    Directory of Open Access Journals (Sweden)

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  13. Autocrine IL-6 mediates pituitary tumor senescence

    Science.gov (United States)

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

    2017-01-01

    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  14. Lactobacillus rhamnosus (LGG regulates IL-10 signaling in the developing murine colon through upregulation of the IL-10R2 receptor subunit.

    Directory of Open Access Journals (Sweden)

    Julie Mirpuri

    Full Text Available The intestinal microflora is critical for normal development, with aberrant colonization increasing the risk for necrotizing enterocolitis (NEC. In contrast, probiotic bacteria have been shown to decrease its incidence. Multiple pro- and anti-inflammatory cytokines have been identified as markers of intestinal inflammation, both in human patients with NEC and in models of immature intestine. Specifically, IL-10 signaling attenuates intestinal responses to gut dysbiosis, and disruption of this pathway exacerbates inflammation in murine models of NEC. However, the effects of probiotics on IL-10 and its signaling pathway, remain poorly defined. Real-time PCR profiling revealed developmental regulation of MIP-2, TNF-α, IL-12, IL-10 and the IL-10R2 subunit of the IL-10 receptor in immature murine colon, while the expression of IL-6 and IL-18 was independent of postnatal age. Enteral administration of the probiotic Lactobacillus rhamnosus GG (LGG down-regulated the expression of TNF-α and MIP-2 and yet failed to alter IL-10 mRNA and protein expression. LGG did however induce mRNA expression of the IL-10R2 subunit of the IL-10 receptor. IL-10 receptor activation has been associated with signal transducer and activator of transcription (STAT 3-dependent induction of members of the suppressors of cytokine signaling (SOCS family. In 2 week-old mice, LGG also induced STAT3 phosphorylation, increased colonic expression of SOCS-3, and attenuated colonic production of MIP-2 and TNF-α. These LGG-dependent changes in phosphoSTAT3, SOCS3, MIP-2 and TNF-α were all inhibited by antibody-mediated blockade of the IL-10 receptor. Thus LGG decreased baseline proinflammatory cytokine expression in the developing colon through upregulation of IL-10 receptor-mediated signaling, most likely due to the combined induction of phospho-STAT3 and SOCS3. Furthermore, LGG-dependent increases in IL-10R2 were associated with reductions in TNF-α, MIP-2 and disease severity in a

  15. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...... allergic encephalitis. Furthermore, aAb-IL-6 carrying mice displayed increased plasma TNFalpha concentrations upon challenge with LPS. Taken together, induction of IL-6 autoantibodies was possible in different mouse strains. The autoantibodies influenced experimental inflammation. This immunotherapeutic...

  16. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media

    NARCIS (Netherlands)

    Emonts, Marieke; Veenhoven, Reinier H.; Wiertsema, Selma P.; Houwing-Duistermaat, Jeanine J.; Walraven, Vanessa; de Groot, Ronald; Hermans, Peter W. M.; Sanders, Elisabeth A. M.

    2007-01-01

    OBJECTIVE. Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS. DNA samples from

  17. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media.

    NARCIS (Netherlands)

    Emonts, M.; Veenhoven, R.H.; Wiertsema, S.P.; Houwing-Duistermaat, J.J.; Walraven, V.; Groot, R. de; Hermans, P.W.M.; Sanders, E.A.M.

    2007-01-01

    OBJECTIVE: Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS: DNA samples from

  18. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media

    NARCIS (Netherlands)

    Emonts, Marieke; Veenhoven, Reinier H.; Wiertsema, Selma P.; Houwing-Duistermaat, Jeanine J.; Walraven, Vanessa; de Groot, Ronald; Hermans, Peter W. M.; Sanders, Elisabeth A. M.

    2007-01-01

    OBJECTIVE. Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS. DNA samples from

  19. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media.

    NARCIS (Netherlands)

    Emonts, M.; Veenhoven, R.H.; Wiertsema, S.P.; Houwing-Duistermaat, J.J.; Walraven, V.; Groot, R. de; Hermans, P.W.M.; Sanders, E.A.M.

    2007-01-01

    OBJECTIVE: Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS: DNA samples from

  20. Critical appraisal of four IL-6 immunoassays.

    Directory of Open Access Journals (Sweden)

    Dana K Thompson

    Full Text Available BACKGROUND: Interleukin-6 (IL-6 contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs, with expected rises in IL-6 concentrations, were used to test the face validity of the various assays. METHODS AND FINDINGS: IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass at time zero, a single infusion of insulin (0.025 U/kg body mass at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD, an Invitrogen Luminex bead-based multiplex panel (LX, an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX, and R&D High Sensitivity ELISA (R&D. IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001 but only ULX correlated (r = 0.31, p = 0.0027 with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049, and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048. CONCLUSION: This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1

  1. Genetic correlation between rheumatoid arthritis and periodontal disease: the role of sex and IL-10.

    Science.gov (United States)

    Azzi, L; Rania, S; Spadari, F; Vinci, R; Manfredini, M; Croveri, F; Boggio, A; Tettamanti, L; Tagliabue, A; Silvestre-Rangil, J; Bellintani, C

    2017-01-01

    The chronic stimulation of the immune system due to the presence of bacterial antigens within periodontal tissues has been associated with several autoimmune diseases, like diabetes mellitus, infective endocarditis or cardiovascular atherosclerosis. The current study aims at evaluating the correlation between Rheumatoid Arthritis (RA) and Periodontal Disease (PD) with special attention to genetic polymorphisms in cytokine expression. A total number of 34 patients affected by RA were recruited. Each of them underwent haematochemical analysis and data were collected for Rheumatoid Factor (RF), Anti-Citrullinated Protein’s Antibody (CCP) and HLA-BDR1. DAS-28 questionnaire for disease activity was fulfilled by the rheumatologist, while a periodontal examination was carried out by the dental clinician and crevicular fluid samples were collected to evaluate the IL-6, IL-10 and VDR polymorphysms. A connection between CCP and IL-10 polymorphisms was found, with IL-10 expressing protecting tendency against periodontal disease when CCP are found in the bloodstream (p=0.0017). Finally, males mainly expressed IL-10 predisposing genes (p=0.046), while females showed a greater tendency to express RF (p=0.014) and CCP (p=0.050). This paper corroborates the idea of a correlation between sex, IL-10 polymorphisms and RA, which should be studied in depth, since recent papers have shown that IL-10 injected into joints seems to decrease inflammation.

  2. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes

    OpenAIRE

    Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Naresh C. Laddha; Thakker, Ami; A. V. Ramachandran; Begum, Rasheedunnisa

    2016-01-01

    Background Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). Objectives The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B tr...

  3. IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat model of preeclampsia.

    Science.gov (United States)

    Harmon, Ashlyn; Cornelius, Denise; Amaral, Lorena; Paige, Adrienne; Herse, Florian; Ibrahim, Tarek; Wallukat, Gerd; Faulkner, Jessica; Moseley, Janae; Dechend, Ralf; LaMarca, Babbette

    2015-01-01

    The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia was used to determine the effects of added interleukin-10 (IL-10) on Tregs and hypertension in response to placental ischemia and how the decrease in these anti-inflammatory factors mediates the pathophysiology of preeclampsia. IL-10 (2.5 ng/kg/d) was infused via osmotic mini-pump implanted intraperitoneally on day 14 of gestation and, at the same time, the RUPP procedure was performed. IL-10 reduced mean arterial pressure (p increasing Tregs (p = 0.043) which led to lower IL-6 and TNF-α (p = 0.008 and p = 0.003), reduced AT1-AA production (p increases Tregs and helps to balance the altered immune system seen during preeclampsia.

  4. Lack of IL-6 during coxsackievirus infection heightens the early immune response resulting in increased severity of chronic autoimmune myocarditis.

    Directory of Open Access Journals (Sweden)

    Maya C Poffenberger

    Full Text Available BACKGROUND: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL-6 is integral to the development of experimental-induced autoimmune myocarditis. However, the function of IL-6 during viral-mediated autoimmunity has yet to be elucidated. METHODS AND RESULTS: To address the requirement of IL-6 during disease induction, IL-6 deficient mice were infected with coxsackievirus B3 (CB3. Following infection, mice lacking IL-6 developed increased chronic autoimmune disease pathology compared to wild type controls without a corresponding change in the level of viral replication in the heart. This increase in disease severity was accompanied by elevated levels of TNF-alpha, MCP-1, IL-10, activated T cells and cardiac infiltrating macrophage/monocytes. Injection of recombinant IL-6 early following infection in the IL-6 deficient mice was sufficient to lower the serum cytokines TNF-alpha and IL-10 as well as the serum chemokines MCP-1, MIP-1beta, RANTES and MIG with a corresponding decrease in the chronic disease pathology strongly suggests an important regulatory role for IL-6 during the early response. CONCLUSIONS: While IL-6 plays a pathogenic role in experimental-induced autoimmune disease, its function following viral-induced autoimmunity is not reprised. By regulating the early immune response and thereby controlling the severity of chronic disease, IL-6 directs the outcome of chronic autoimmune myocarditis.

  5. Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase.

    Science.gov (United States)

    Barros, P O; Cassano, T; Hygino, J; Ferreira, T B; Centurião, N; Kasahara, T M; Andrade, R M; Linhares, U C; Andrade, A F B; Vasconcelos, C C F; Alvarenga, R; Marignier, R; Bento, C A M

    2016-03-01

    T helper type 17 (Th17) cytokines have been implicated in the pathogenesis of neuromyelitis optica (NMO). As humanized anti-interleukin (IL)-6R (tocilizumab) immunoglobulin (Ig)G has been used as disease-modifying therapy for NMO, the objective of our study was to investigate the role of endogenous IL-6 on NMO-derived CD4(+) T cell behaviour. High production of IL-6, IL-17 and IL-21 by CD4(+) T-cells was detected in NMO patients. Further, IL-21 and IL-6 levels were related directly to the level of neurological disabilities. The addition of anti-IL-6R IgG not only reduced directly the production of these cytokines, but also almost abolished the ability of activated autologous monocytes in enhancing IL-6, IL-17 and IL-21 release by CD4(+) T cells. In contrast, the production of IL-10 was amplified in those cell cultures. Further, anti-IL-6R monoclonal antibodies (mAb) also potentiated the ability of glucocorticoid in reducing Th17 cytokines. Finally, the in-vivo and in-vitro IL-6 levels were significantly higher among those patients who experienced clinical relapse during 2-year follow-up. In summary, our results suggest a deleterious role of IL-6 in NMO by favouring, at least in part, the expansion of corticoid-resistant Th17 cells.

  6. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Science.gov (United States)

    Siegel, Andrea M; Herskowitz, Jeremy H; Speck, Samuel H

    2008-04-01

    Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a

  7. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

    Full Text Available Murine gammaherpesvirus 68 (MHV68 establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV. EBV encodes an interleukin-10 (IL-10 homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25 and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis

  8. IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke.

    Science.gov (United States)

    Fernández-Cadenas, Israel; Del Río-Espínola, Alberto; Giralt, Dolors; Domingues-Montanari, Sophie; Quiroga, Adoracion; Mendióroz, Maite; Ruíz, Agustin; Ribó, Marc; Serena, Joaquin; Obach, Victor; Freijo, Mari Mar; Martí-Fábregas, Joan; Delgado, Pilar; Montaner, Joan

    2012-10-01

    There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration. A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity. After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.

  9. Sodium Butyrate Reduces Colitogenic Immunoglobulin A-Coated Bacteria and Modifies the Composition of Microbiota in IL-10 Deficient Mice.

    Science.gov (United States)

    Zhang, Tenghui; Ding, Chao; Zhao, Mingli; Dai, Xujie; Yang, Jianbo; Li, Yi; Gu, Lili; Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Li, Ning; Li, Jieshou

    2016-11-24

    High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving inflammatory bowel disease (IBD). We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL)-10(-/-) mice. At 8 weeks of age, mice were allocated into three groups (n = 4/group): normal (C57BL/6), IL-10(-/-), and IL-10(-/-) treated with sodium butyrate (100 mM). Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF)-α and IL-6 in IL-10(-/-) mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10(-/-) mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10(-/-) mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10(-/-) mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10(-/-) mice.

  10. Research Advancement on Exercise and IL-6%运动与IL-6的研究进展

    Institute of Scientific and Technical Information of China (English)

    王今越; 丁树哲; 刘伟; 王小虹

    2007-01-01

    通过文献资料调研,总结并分析以往至最新的IL-6研究成果,从运动与肌源性IL-6 、运动与不同类型肌纤维IL-6的生成、运动训练与IL-6IL-6R系统、运动模式与IL-6、糖代谢与IL-6IL-6与抗氧化剂VC、VE、IL-6与IL-8、IL-6与SOCS-3几个方面论述运动介导下,IL-6的生成特点、影响因素和生物学功能.

  11. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes

    Science.gov (United States)

    Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C.; Thakker, Ami; Ramachandran, A. V.; Begum, Rasheedunnisa

    2016-01-01

    Background Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). Objectives The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. Methods PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Results Our results show significant association of both structural and promoter polymorphisms of NPY (pLDL levels (p = 0.01). Conclusion The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population. PMID:27749914

  12. The IL1B-511 Polymorphism (rs16944 AA Genotype Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

    Directory of Open Access Journals (Sweden)

    Ramcés Falfán-Valencia

    2012-01-01

    Full Text Available Aspirin exacerbated respiratory disease (AERD is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1 inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO route, inducing increased synthesis of leukotrienes (LT. The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073 and IL1B-511 (rs16944 polymorphisms in AERD, aspirin-tolerant asthma (ATA, and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944. Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, =0.018, OR 2.98, and 95% CI 1.17–7.82. This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1 is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  13. Predição das concentrações plasmáticas de IL-1B, IL-6 e TNF-α por agrupamentos de fatores de risco cardiovascular em adolescentes.

    OpenAIRE

    Silva, Carla Teixeira

    2014-01-01

    Programa de Pós-Graduação em Saúde e Nutrição. Escola de Nutrição, Universidade Federal de Ouro Preto. As doenças cardiovasculares (DCV) são as principais causas de mobi-mortalidade em todo o mundo e estão bem relacionadas a diversos fatores de risco cardiovascular tradicionais (RCV), incluindo obesidade central, resistência à insulina (RI), intolerância à glicose, dislipidemias e hipertensão arterial sistêmica (HAS). A inflamação tem sido associada a muitos destes fatores de risco, aprese...

  14. IL-10 promoter polymorphisms affect IL-10 production and associate with susceptibility to acute myeloid leukemia.

    Science.gov (United States)

    Chenjiao, Yao; Zili, Fan; Haibin, Chen; Ying, Liu; Sheng, Xiao; Lihua, Huang; Wei, Du

    2013-03-01

    We investigated the possible association of Interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 AML patients and 137 gender- and age-matched controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results revealed that the -819AA genotype frequencies and the -819A allele frequencies of AML group were higher than the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in AML group (75.6% vs 63.9%, P<0.05). The IL-10 mRNA expression of AML patients and controls with different genotype was detected by Real-time quantitative Polymerase Chain Reaction (RT-PCR). IL-10 mRNA expression in incipient AML patients increased obviously compared with the non-tumor group and remission group (P<0.05). Further analysis suggested that the IL-10 mRNA expression of TA/TA genotype was the lowest and CC/CC genotype was the highest; the haploid TA and genotype TA/TA may be associated with AML. The research suggested the IL-10 SNPs at -819 and -592 sites were associated with AML and may affect the IL-10 mRNA expression in AML patients in Han people of Hunan province.

  15. Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes.

    Science.gov (United States)

    Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C; Thakker, Ami; Ramachandran, A V; Begum, Rasheedunnisa

    2016-01-01

    Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Our results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10-5, p = 6.04 x 10-9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01). The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population.

  16. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    BACKGROUND: Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have higher IL-6 levels, but few data are available on factors associated with circulating IL-6. METHODS......: Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4(+) cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART...... education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4(+) cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking...

  17. In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Borch, T S; Holmstrup, Palle; Bendtzen, K

    2010-01-01

    Generalized aggressive periodontitis (GAgP) is an inflammatory condition resulting in destruction of tooth-supporting tissues. We examined the production of IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IL-12 and IL-10 in cultures of peripheral mononuclear cells (MNC) from 10 patients...... from two donors free of disease were stimulated with this bacterium in the presence of the various patient and control sera. An elevated IL-6 and TNF-alpha response was observed in the presence of patient sera (P ... occurs in GAgP, and that pro-inflammatory serum factors play an essential role in the response....

  18. IL-6 predicts organ dysfunction and mortality in patients with multiple injuries

    Science.gov (United States)

    Frink, Michael; van Griensven, Martijn; Kobbe, Philipp; Brin, Thomas; Zeckey, Christian; Vaske, Bernhard; Krettek, Christian; Hildebrand, Frank

    2009-01-01

    Background Although therapeutic concepts of patients with major trauma have improved during recent years, organ dysfunction still remains a frequent complication during clinical course in intensive care units. It has previously been shown that cytokines are upregulated under stress conditions such as trauma or sepsis. However, it is still debatable if cytokines are adequate parameters to describe the current state of trauma patients. To elucidate the relevance of cytokines, we investigated if cytokines predict development of multiple organ dysfunction syndrome (MODS) or outcome. Methods A total of 143 patients with an injury severity score ≥ 16, between 16 and 65 years, admitted to the Hannover Medical School Level 1 Trauma Center between January 1997 and December 2001 were prospectively included in this study. Marshall Score for MODS was calculated for at least 14 days and plasma levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 were measured. To determine the association between cytokine levels and development of MODS the Spearman rank correlation coefficient was calculated and logistic regression and analysis were performed. Results and Discussion Patients with MODS had increased plasma levels of IL-6, IL-8 and IL-10. IL-6 predicted development of MODS with an overall accuracy of 84.7% (specificity: 98.3%, sensitivity: 16.7%). The threshold value for development of MODS was 761.7 pg/ml and 2176.0 pg/ml for mortality during the in patient time. Conclusion We conclude that plasma IL-6 levels predict mortality and that they are a useful tool to identify patients who are at risk for development of MODS. PMID:19781105

  19. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

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    Magali Silveira Monteiro Ribeiro

    2016-01-01

    Full Text Available Background: Although the interleukin-1 (IL-1 plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944, IL1B +3954C>T (rs1143634, and IL1RN intron 2 variable number tandem repeat (VNTR (rs2234663 polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43 and chronic (chronic periodontitis [CP], n = 52 periodontitis, and controls (n = 50 were genotyped by polymerase chain reaction (PCR (IL1RN intron 2 VNTR or PCR-restriction fragment length polymorphism (PCR-RFLP (IL1B-511 C>T and IL1B + 3954C>T techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher′s exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84, particularly in smokers (OR = 4.43 and females (OR = 6.00. The minor alleles IL1RNFNx012 and FNx013 increased the risk of AgP (OR = 2.18, especially the IL1RNFNx012FNx012 genotype among  white Brazilians (OR = 7.80. Individuals with the combinations of the IL1B + 3954T and IL1RNFNx012 or FNx013-containing genotypes were at increased risk of developing CP (OR = 4.50. Considering the three polymorphisms (rs16944, rs1143634, and rs2234663, the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41 and CP (OR = 6.39, respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals.

  20. Differential association of RANTES-403 and IL-1B-1464 polymorphisms on histological subtypes in male Korean patients with gastric cancer.

    Science.gov (United States)

    Kim, Juwon; Kim, Jong-Won; Kim, Yoonjung; Lee, Kyung-A

    2014-04-01

    The aims of this study were to elucidate the association between RANTES-403 and an increased risk of gastric cancer in Korean males and to investigate the gene-gene interaction between IL-1B and RANTES. In total, 218 male patients with gastric cancer (114 diffuse types, 97 intestinal types, and 7 mixed types) and 377 male controls were included. RANTES-403 was genotyped, and age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression. A multifactor dimensionality reduction (MDR) test with three-way split interval validation confirmed by likelihood ratio and permutation analysis was carried out. A significant increase in the risk of gastric cancer for the intestinal-type group was observed for IL-1B-1464G carriers (OR = 2.535; 95% CI = 1.121-5.732; P = 0.02) as well as for those with IL-1B-1464 CG (OR = 2.342; 95% CI = 0.998-5.500; P = 0.05) or IL-1B-1464 GG (OR = 2.819; 95% CI = 1.170-6.793; P = 0.02). For the RANTES-403 genotype, there was no significant difference in the risk of gastric cancer between the overall gastric cancer and the control groups. When further stratified according to histological types, RANTES-403A carriers (OR = 1.743; 95% CI = 1.086-2.798; P = 0.021) or heterozygotes (OR = 1.791; 95% CI = 1.092-2.935; P = 0.021) showed increased risk for developing diffuse-type gastric cancer. MDR revealed a three-way locus-locus interaction between RANTES-403AA, IL-1B-1464GG, and IL-1B-511CT for diffuse-type gastric cancer in Korean males. We demonstrated that RANTES-403 was significantly associated with the risk of developing diffuse-type gastric cancer in men and found a possible gene-gene interaction between RANTES and IL-1B polymorphisms in gastric cancer carcinogenesis.

  1. Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.

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    Carmen A Ambarus

    Full Text Available BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs. Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4. In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2. The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.

  2. Interleukin-10 (IL-10) polymorphisms are associated with IL-10 production and clinical malaria in young children.

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    Zhang, Guicheng; Manaca, Maria Nelia; McNamara-Smith, Michelle; Mayor, Alfredo; Nhabomba, Augusto; Berthoud, Tamara Katherine; Khoo, Siew-Kim; Wiertsema, Selma; Aguilar, Ruth; Barbosa, Arnoldo; Quintó, Llorenç; Candelaria, Pierre; Schultz, En Nee; Hayden, Catherine M; Goldblatt, Jack; Guinovart, Caterina; Alonso, Pedro L; Lesouëf, Peter N; Dobaño, Carlota

    2012-07-01

    The role of interleukin-10 (IL-10) in malaria remains poorly characterized. The aims of this study were to investigate (i) whether genetic variants of the IL-10 gene influence IL-10 production and (ii) whether IL-10 production as well as the genotypes and haplotypes of the IL-10 gene in young children and their mothers are associated with the incidence of clinical malaria in young children. We genotyped three IL-10 single nucleotide polymorphisms in 240 children and their mothers from a longitudinal prospective cohort and assessed the IL-10 production by maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs). Clinical episodes of Plasmodium falciparum malaria in the children were documented until the second year of life. The polymorphism IL-10 A-1082G (GCC haplotype of three SNPs in IL-10) in children was associated with IL-10 production levels by CBMC cultured with P. falciparum-infected erythrocytes (P = 0.043), with the G allele linked to low IL-10 production capacity. The G allele in children was also significantly associated with a decreased risk for clinical malaria infection in their second year of life (P = 0.016). Furthermore, IL-10 levels measured in maternal PBMCs cultured with infected erythrocytes were associated with increased risk of malaria infection in young children (P IL-10 polymorphisms and IL-10 production capacity were associated with clinical malaria infections in young children. High IL-10 production capacity inherited from parents may diminish immunological protection against P. falciparum infection, thereby being a risk for increased malaria morbidity.

  3. Effect of IFN-γ/IL-10 on IL-10 Receptor Expression of Human Decidual Stromal Cells in Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Chang-ying XING; Sui-qi GUI

    2006-01-01

    Objective To study the role of IFN-γ /IL-10 cytokines on IL-10 receptor gene and protein expression of human decidual stromal cells(DSC) in human early pregnancy in vitro.Methods Human DSC was isolated and cultured in vitro, and the expression of IL-10R1 and IL-10R2 gene was analyzed after cells had been treated with TH2-type cytokines IL-10 and TH1-type cytokines IFN-γ within 60 min with semiquantitative reverse transcriptase-PCR, then the influence of IL-10 and IFN-γ on expression of IL-10R protein was examined by first trimester DSC using flow cytometry. In addition,the vitality of DSC was detected by MTT.Results IL-10R1 mRNA levels of DSC treated with IL-10 (10 ng/ml) reached the peak level within 15 min, and were significantly lower at 30 min, then were not detected at 45 min. The expression of IL-10R1 were induced to moderate level by IFN-γ(10 ng/ml)within 30 min, and reduced to undetected levels at 60 min. There was no significant difference of IL-10R2 expression (P>0.05) between treated and not with the abovementioned cytokines. The IL-10R protein expression and vitality of DSC were significantly enhanced by IL-10 (10 ng/ml) and IFN-γ (10 ng/ml) which treated DSC 48 h (P<0. 05).Conclusion IL-10 and IFN-γ may play an important role of biologic function in early pregnancy by influencing IL-10R expression of DSC.

  4. Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms.

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    Engler, H; Brendt, P; Wischermann, J; Wegner, A; Röhling, R; Schoemberg, T; Meyer, U; Gold, R; Peters, J; Benson, S; Schedlowski, M

    2017-01-31

    Systemic inflammation is accompanied by profound behavioral and mood changes that resemble symptoms of depression. Findings in animals suggest that pro-inflammatory cytokines released by activated immune cells in the periphery evoke these behavioral symptoms by driving inflammatory changes in the brain. However, experimental data in humans are lacking. Here we demonstrate in healthy male volunteers (10 endotoxin treated, 8 placebo treated) that intravenous administration of low-dose endotoxin (0.8 ng/kg body weight), a prototypical pathogen-associated molecular pattern that activates the innate immune system, not only induces a significant increase in peripheral blood cytokine concentrations (that is, tumor necrosis factor-α, interleukin (IL)-6, IL-10) but also results, with some latency, in a robust and selective increase of IL-6 in the cerebrospinal fluid (CSF). Moreover, we found a strong association between the endotoxin-induced increase of IL-6 in the CSF and the severity of mood impairment, with larger increases in CSF IL-6 concentration followed by a greater deterioration in mood. Taken together, these findings suggest that the appearance of depressive symptoms in inflammatory conditions might be primarily linked to an increase in central IL-6 concentration, identifying IL-6 as a potential therapeutic target in mood disorders.Molecular Psychiatry advance online publication, 31 January 2017; doi:10.1038/mp.2016.264.

  5. Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

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    P. Mommsen

    2012-01-01

    Full Text Available Splenic immune function is known to be depressed following hemorrhage. The present study investigates the effects of femoral shaft fracture, isolated or in combination with hemorrhage, on early stage cytokine production capacity of splenocytes and observes the role of IL-6 under these conditions. Male IL-6 knockout (IL-6−/− and wild-type mice (WT were randomly divided into three groups: sham (S, isolated femoral fracture (Fx, and femoral fracture + volume controlled hemorrhage (TH-Fx (=6 per group. Animals were sacrificed four hours after induction of hemorrhage and fracture. Cytokine release (TNF-α, IL-6, and IL-10 of isolated and LPS-stimulated splenocytes was determined by cytometric bead array. Femoral fracture with or without hemorrhage caused a suppression of in vitro cytokine production capacity of splenocytes at an early posttraumatic stage in WT and IL-6−/−. In the absence of IL-6, the profile of splenic cytokine secretion is significantly altered, identifying this cytokine as a potential therapeutic target to modulate the posttraumatic immune response.

  6. Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth.

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    Velez, Digna R; Fortunato, Stephen J; Williams, Scott M; Menon, Ramkumar

    2008-06-01

    Spontaneous preterm birth (PTB-gestational age rs1800797, rs1800796 and rs1800795; in IL-6R markers rs4075015, rs4601580, rs4645618, rs6687726 and rs7549338 and markers rs4845623, rs4537545 and rs4845625. In conclusion, our results suggest that IL-6 AF concentration, in situations of PTB, result from variation in IL-6 and more importantly IL-6R.

  7. PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS.

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    Domingues, Wilson; Kanunfre, Kelly Aparecida; Rodrigues, Jonatas Cristian; Teixeira, Leandro Emidio; Yamamoto, Lidia; Okay, Thelma Suely

    2016-01-01

    Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation.

  8. P2X7-dependent, but differentially regulated release of IL-6, CCL2, and TNF-alpha in cultured mouse microglia

    NARCIS (Netherlands)

    Shieh, Chu-Hsin; Heinrich, Annette; Serchov, Tsvetan; van Calker, Dietrich; Biber, Knut

    2014-01-01

    ATP is an important regulator of microglia and its effects on microglial cytokine release are currently discussed as important contributors in a variety of brain diseases. We here analyzed the effects of ATP on the production of six inflammatory mediators (IL-6, IL-10, CCL2, IFN-gamma, TNF-alpha, an

  9. P2X7-dependent, but differentially regulated release of IL-6, CCL2, and TNF-alpha in cultured mouse microglia

    NARCIS (Netherlands)

    Shieh, Chu-Hsin; Heinrich, Annette; Serchov, Tsvetan; van Calker, Dietrich; Biber, Knut

    ATP is an important regulator of microglia and its effects on microglial cytokine release are currently discussed as important contributors in a variety of brain diseases. We here analyzed the effects of ATP on the production of six inflammatory mediators (IL-6, IL-10, CCL2, IFN-gamma, TNF-alpha,

  10. Suppressor of cytokine signaling 3 inhibits LPS-induced IL-6 expression in osteoblasts by suppressing CCAAT/enhancer-binding protein ß activity

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    Suppressors of cytokine signaling 3 (SOCS3) is an important intracellular regulator of TLR4 signaling and has been implicated in several inflammatory diseases. Although SOCS3 seems to contribute to the balance between the pro-inflammatory effects of IL-6 and antiinflammatory signaling of IL-10 by ne...

  11. B cell activating factor (BAFF) selects IL-10(-)B cells over IL-10(+)B cells during inflammatory responses.

    Science.gov (United States)

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-02-12

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10(-)B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10(+) Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10(+)B cells over IL-10(-)B cells under noninflammatory conditions in vitro, whereas it expanded IL-10(-)B cells over IL-10(+)B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10(-)B cells over IL-10(+)B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10(-)B cells over IL-10(+) regulatory B cells via BAFF receptors in inflammatory responses.

  12. In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Borch, T S; Holmstrup, Palle; Bendtzen, K;

    2010-01-01

    the participants' inherent oral flora. The P. gingivalis -induced production of IL-6 was approximately 2.5-fold higher in patients with GAgP than in healthy controls (P TNF-alpha production was non-significantly elevated. IL-1beta production induced by P. gingivalis, as all cytokine......Generalized aggressive periodontitis (GAgP) is an inflammatory condition resulting in destruction of tooth-supporting tissues. We examined the production of IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IL-12 and IL-10 in cultures of peripheral mononuclear cells (MNC) from 10 patients...... from two donors free of disease were stimulated with this bacterium in the presence of the various patient and control sera. An elevated IL-6 and TNF-alpha response was observed in the presence of patient sera (P

  13. Sodium Butyrate Reduces Colitogenic Immunoglobulin A-Coated Bacteria and Modifies the Composition of Microbiota in IL-10 Deficient Mice

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    Tenghui Zhang

    2016-11-01

    Full Text Available High levels of immunoglobulin A (IgA-coated bacteria may have a role in driving inflammatory bowel disease (IBD. We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL-10−/− mice. At 8 weeks of age, mice were allocated into three groups (n = 4/group: normal (C57BL/6, IL-10−/−, and IL-10−/− treated with sodium butyrate (100 mM. Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF-α and IL-6 in IL-10−/− mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10−/− mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10−/− mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10−/− mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10−/− mice.

  14. Rosiglitazone regulates IL-6-stimulated lipolysis in porcine adipocytes.

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    Yang, Yongqing; Yang, Gongshe

    2010-10-01

    Interleukin (IL)-6, a proinflammatory cytokine, stimulates adipocyte lipolysis and induces insulin resistance in obese and diabetic subjects. However, the effects of the anti-diabetic drug rosiglitazone on IL-6-stimulated lipolysis and the underlying molecular mechanism are largely unknown. In this study, we demonstrated that rosiglitazone suppressed IL-6-stimulated lipolysis in differentiated porcine adipocytes by inactivation of extracellular signal-related kinase (ERK). Meanwhile, rosiglitazone enhanced the lipolysis response of adipocytes to isoprenaline. In addition, rosiglitazone significantly reversed IL-6-induced down-regulation of several genes such as perilipin A, peroxisome proliferators activated receptor gamma (PPARγ), and fatty acid synthetase, as well as the up-regulation of IL-6 mRNA. However, mRNA expression of PPARγ coactivator-1 alpha (PCG-1α) was enhanced by rosiglitazone in IL-6-stimulated adipocytes. These results indicate that rosiglitazone suppresses IL-6-stimulated lipolysis in porcine adipocytes through multiple molecular mechanisms.

  15. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.

    Science.gov (United States)

    Sales-Marques, Carolinne; Cardoso, Cynthia Chester; Alvarado-Arnez, Lucia Elena; Illaramendi, Ximena; Sales, Anna Maria; Hacker, Mariana de Andréa; Barbosa, Mayara Garcia de Mattos; Nery, José Augusto da Costa; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-07-01

    The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.

  16. IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

    Science.gov (United States)

    Estrada-Jiménez, Tania; Sedeño-Monge, Virginia; Moreno, Margarita; Manjarrez, María del Consuelo; González-Ochoa, Guadalupe; Millán-Pérez Peña, Lourdes

    2017-01-01

    Background Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. Objective To explore the association of cytokine and socs levels with disease severity in dengue patients. Methods Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. Results Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p 199.8-fold), socs1 (134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. Conclusion Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity. PMID:28827898

  17. IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

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    Lilian Karem Flores-Mendoza

    2017-01-01

    Full Text Available Background. Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. Objective. To explore the association of cytokine and socs levels with disease severity in dengue patients. Methods. Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN- γ, and tumor necrosis factor- (TNF- α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. Results. Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF with respect to those with dengue fever (DF (p199.8-fold, socs1 (134 pg/ml have the highest sensitivity and specificity to discriminate between DF and DHF. Conclusion. Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.

  18. Insights into deregulated TNF and IL-10 production in malaria

    DEFF Research Database (Denmark)

    Boeuf, Philippe S; Loizon, Séverine; Awandare, Gordon A

    2012-01-01

    ABSTRACT: BACKGROUND: Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized...... by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about...... the activation status of those cells in SMA patients. METHODS: The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM...

  19. Higher IL-6 and IL6:IGF Ratio in Patients with Barth Syndrome

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    Wilson Lori D

    2012-06-01

    Full Text Available Abstract Background Barth Syndrome (BTHS is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5. The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients. Methods Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs and 14 healthy control males (8 - 21 yrs was analyzed for two growth factors: IGF-1 (bound and free and Growth Hormone (GH; and two inflammatory cytokines IL-6 and TNF-α using high-sensitivity enzyme-linked immunosorbent assays. Results The average IL-6 and IL6:IGF ratio levels were significantly higher in the BTHS (p = 0.046 and 0.02 respectively. As for GH, there was a significant group by age interaction (p = 0.01, such that GH was lower for BTHS patients under the age of 14.4 years and higher than controls after age 14.4 years. TNF-α levels were not significantly different, however, the TNF-α:GH was lower in BTHS patients than controls (p = 0.01. Conclusions Comparison of two anabolic growth mediators, IGF and GH, and two catabolic cytokines, IL-6 and TNF-α, in BTHS patients and healthy age-matched controls demonstrated a potential imbalance in inflammatory cytokines and anabolic growth factors. Higher rates of IL-6 (all ages and lower GH levels were observed in BTHS patients (under age 14.5 compared to controls. These findings may implicate inflammatory processes in the catabolic nature of Barth Syndrome pathology as well as provide a link to mitochondrial function. Furthermore, interactions between growth factors, testosterone and inflammatory mediators may explain some of the variability in cardiac and skeletal myopathies seen

  20. PEGylated IL-10 Activates Kupffer Cells to Control Hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Ivan H Chan

    Full Text Available Interleukin-10 (IL-10 is a multifunctional cytokine that exerts potent context specific immunostimulatory and immunosuppressive effects. We have investigated the mechanism by which PEGylated rIL-10 regulates plasma cholesterol in mice and humans. In agreement with previous work on rIL-10, we report that PEGylated rIL-10 harnesses the myeloid immune system to control total plasma cholesterol levels. We have discovered that PEG-rMuIL-10's dramatic lowering of plasma cholesterol is dependent on phagocytotic cells. In particular, PEG-rHuIL-10 enhances cholesterol uptake by Kupffer cells. In addition, removal of phagocytotic cells dramatically increases plasma cholesterol levels, suggesting for the first time that immunological cells are implicitly involved in regulating total cholesterol levels. These data suggest that treatment with PEG-rIL-10 potentiates endogenous cholesterol regulating cell populations not currently targeted by standard of care therapeutics. Furthermore, we show that IL-10's increase of Kupffer cell cholesterol phagocytosis is concomitant with decreases in liver cholesterol and triglycerides. This leads to the reversal of early periportal liver fibrosis and facilitates the restoration of liver health. These data recommend PEG-rIL-10 for evaluation in the treatment of fatty liver disease and preventing its progression to non-alcoholic steatohepatitis. In direct confirmation of our in vivo findings in the treatment of hypercholesterolemic mice with PEG-rMuIL-10, we report that treatment of hypercholesterolemic cancer patients with PEG-rHuIL-10 lowers total plasma cholesterol by up to 50%. Taken together these data suggest that PEG-rIL-10's cholesterol regulating biology is consistent between mice and humans.

  1. Encephalitozoon intestinalis inhibits dendritic cell differentiation through an IL-6-dependent mechanism

    Directory of Open Access Journals (Sweden)

    Carmen Elisa Bernal Silva

    2016-02-01

    Full Text Available AbstractMicrosporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNg, CD4+ and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei, a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1b or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNg secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNg secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development towards cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation.

  2. Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

    Science.gov (United States)

    Jung, Bock-Gie; Wang, Xisheng; Yi, Na; Ma, Justin; Turner, Joanne; Samten, Buka

    2017-01-01

    As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production. ESAT-6 but not Pam3CSK4 induced IL-6 by TLR2 knockout BMDM. ESAT-6 induced phosphorylation and DNA binding of STAT3 and this was blocked by STAT3 inhibitors but not by rapamycin. STAT3 inhibitors suppressed ESAT-6-induced IL-6 transcription and secretion without affecting cell viability. This was confirmed by silencing STAT3 in macrophages. Blocking neither IL-6Rα/IL-6 nor IL-10 affected ESAT-6-induced STAT3 activation and IL-6 production. Infection of BMDM and human macrophages with Mtb with esat-6 deletion induced diminished STAT3 activation and reduced IL-6 production compared to wild type and esat-6 complemented Mtb strains. Administration of ESAT-6 but not CFP10 induced STAT3 phosphorylation and IL-6 expression in the mouse lungs, consistent with expression of ESAT-6, IL-6 and phosphorylated-STAT3 in Mtb-infected mouse lungs. We conclude that ESAT-6 stimulates macrophage IL-6 production through STAT3 activation. PMID:28106119

  3. STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

    Science.gov (United States)

    Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2015-09-01

    Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

  4. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Ricardo C Ferreira

    2013-04-01

    Full Text Available Inflammation, which is directly regulated by interleukin-6 (IL-6 signaling, is implicated in the etiology of several chronic diseases. Although a common, non-synonymous variant in the IL-6 receptor gene (IL6R Asp358Ala; rs2228145 A>C is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD, rheumatoid arthritis (RA, atrial fibrillation (AF, abdominal aortic aneurysm (AAA, and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known. Here we provide evidence for the association of this non-synonymous variant with the risk of type 1 diabetes (T1D in two independent populations and confirm that rs2228145 is the major determinant of the concentration of circulating soluble IL-6R (sIL-6R levels (34.6% increase in sIL-6R per copy of the minor allele 358Ala; rs2228145 [C]. To further investigate the molecular mechanism of this variant, we analyzed expression of IL-6R in peripheral blood mononuclear cells (PBMCs in 128 volunteers from the Cambridge BioResource. We demonstrate that, although 358Ala increases transcription of the soluble IL6R isoform (P = 8.3×10⁻²² and not the membrane-bound isoform, 358Ala reduces surface expression of IL-6R on CD4+ T cells and monocytes (up to 28% reduction per allele; P≤5.6×10⁻²². Importantly, reduced expression of membrane-bound IL-6R resulted in impaired IL-6 responsiveness, as measured by decreased phosphorylation of the transcription factors STAT3 and STAT1 following stimulation with IL-6 (P≤5.2×10⁻⁷. Our findings elucidate the regulation of IL-6 signaling by IL-6R, which is causally relevant to several complex diseases, identify mechanisms for new approaches to target the IL-6/IL-6R axis, and anticipate differences in treatment response to IL-6 therapies based on this common IL6R variant.

  5. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist....... MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates...... corresponding to fold differences (FDs) in IL-6 were calculated. Demographics (age, gender, race, BMI) and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different ART regimens) were investigated in all three trials. In SMART (N=4498), smoking, comorbidities (CVD, diabetes, hepatitis B...

  6. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...

  7. Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

    Directory of Open Access Journals (Sweden)

    Fernández-Tilapa Gloria

    2010-10-01

    Full Text Available Abstract Background The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area. Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. Methods We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. Results Sixty-two point seven (62.7% of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4% and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively. The subjects carrying -31T (rs1143627 -31 C>T were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8. The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8 but not with gastric ulcer. Conclusions The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was

  8. Sterile trauma to normal human dermis invariably induces IL1beta, IL6 and IL8 in an innate response to "danger".

    Science.gov (United States)

    Sjögren, Florence; Anderson, Chris

    2009-01-01

    Microdialysis allows the study of the local production and temporal resolution of cytokines in living skin. Samples were taken from the normal skin of 10 healthy subjects for 24-28 h after insertion of a concentric microdialysis catheter, and analysed with a Luminex bead-based assay. Interleukin-1 beta (IL1b), IL6 and IL8 were seen in all subjects at all time-points after the first hour. Levels peaked at 5-8 h, equilibrating to lower levels at 24 h. Immunohistological double staining for human leukocyte antigen (HLA)-DR and intracellular cytokines on biopsies taken after catheter removal showed many stained cells in the dermis, in contrast to the few cells stained in the epidermis. This study demonstrates the reactive capability of the dermis when provoked separately from the epidermis. The production of IL1b, IL6 and IL8 occurs invariably in what can be termed an innate, dermal response to "danger"; in this case in the form of sterile needle trauma.

  9. IL-1β and IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype

    Science.gov (United States)

    Zhang, Junlong; Shen, Beilei; Huang, Zhuochun; Tan, Chunyu; Baan, Carla C.

    2017-01-01

    Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1β, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1β) were measured in sera of familial SLE patients (n = 3), noninherited SLE patients (n = 108), and healthy controls (n = 80). Results. Three familial SLE patients and 5 noninherited SLE cases are with features of RF+IgE+. These RF+IgE+ SLE patients expressed significantly higher levels of IL-1β and IL-6 than the other SLE patients (P < 0.05). IL-6 correlated with both IgE and IL-1β levels in RF+IgE+ SLE patients (r2 = 0.583, P = 0.027; r2 = 0.847, P = 0.001), and IgE also correlated with IL-1β (r2 = 0.567, P = 0.031). Conclusion. Both IL-1β and IL-6 are highly expressed cytokines in RF+IgE+ SLE subtype which may be related to the pathogenesis of this special SLE subtype and provide accurate treatment strategy by neutralizing IL-1β and IL-6. PMID:28286780

  10. IL-10 control of dendritic cells in the skin

    NARCIS (Netherlands)

    B.E. Clausen (Bjorn); M.J.H. Girard-Madoux (Mathilde)

    2013-01-01

    textabstractInterleukin-10 (IL-10) is a potent immunomodulatory cytokine, whose cellular targets have not yet been precisely identified. Mice bearing a dendritic cell (DC)-specific defect in the IL-10 receptor mice exhibit exaggerated T-cell reactivation in the skin, highlighting a key function of D

  11. Serum IL-6 level and associated factors: hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  12. Recent advances in neutralizing the IL-6 pathway in arthritis

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    Charles J Malemud

    2009-10-01

    Full Text Available Charles J MalemudDivision of Rheumatic Diseases, Case Western Reserve University, School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USAAbstract: Recent advances in understanding the mechanism(s of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA, psoriatic arthritis (PsA, ankylosing spondylitis (AS and osteoarthritis (OA. IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R. Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines.Keywords: interleukin-6, interleukin-6/interleukin-6 receptor/glycoprotein 130, JAK/STAT pathway, SAP/MAPK pathway, osteoarthritis, rheumatoid arthritis

  13. IL-6 Potentiates Tumor Resistance to Photodynamic Therapy (PDT)

    Science.gov (United States)

    Brackett, Craig M.; Owczarczak, Barbara; Ramsey, Kimberley; Maier, Patricia G.; Gollnick, Sandra O.

    2013-01-01

    Background and Objective Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. Study Design/Materials and Methods In the current study we used mice deficient for IL-6, Il6−/−, to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. Results Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6−/− mice 24 hours following PDT. Conclusions The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered. PMID:22057495

  14. Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease.

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    Cecília Durães

    Full Text Available Autoimmune thyroid disease (AITD comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.Polymorphisms in the IL6-174 G/C (rs1800795, TNFA-308 G/A (rs1800629, IL1B-511 C/T (rs16944, and IFNGR1-56 T/C (rs2234711 genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37-2.43, p-value = 4.4×10(-5 and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2×10(-5 models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06-1.54, p-value = 8.9×10(-3. The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19-2.87, p-value = 7.0×10(-3 and log-additive (OR = 1.69, CI = 1.17-2.44, p-value = 6.6×10(-3 models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59.This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the

  15. Preparation and validation of radio iodinated recombinant human IL-10 for the measurement of natural human antibodies against IL-10

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Svenson, Morten

    2009-01-01

    activity of 75 cpm/pg. Validation of the tracer confirmed preserved antibody epitopes and receptor binding ability. A robust Radio Immuno Assay (RIA) was developed and validated to detect natural human anti-IL-10 antibodies based on the formation of (125)I-labeled IL-10-IgG complexes in solution...

  16. IL6 gene promoter polymorphisms and type 2 diabetes

    DEFF Research Database (Denmark)

    Huth, Cornelia; Heid, Iris M; Vollmert, Caren;

    2006-01-01

    Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

  17. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  18. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  19. IL-10 Function, Regulation, and in Bacterial Keratitis

    OpenAIRE

    Hazlett, Linda D.; Jiang, Xiaoyu; McClellan, Sharon A.

    2014-01-01

    The immune system protects the host from pathogenic microbes, but tight regulation of the evoked response is requisite to limit bystander damage. The interleukin (IL)-10 family of cytokines, composed of 9 members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and 3 distantly related members, IL-28A, IL-28B, and IL-29, plays a central role in this regulation. IL-10 family cytokines emerged before the adaptive immune response and elicit diverse host defense mechanisms, especially from epithelial ce...

  20. IL-10-Producing CD1dhiCD5+ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients

    Science.gov (United States)

    Chen, Ying; Li, Chao; Lu, Yiping; Zhuang, Huiying; Gu, Weijia; Liu, Bo; Liu, Fangwei; Sun, Jinkai; Yan, Bo; Weng, Dong; Chen, Jie

    2017-01-01

    Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of Bregs in silicosis patients (SP). In this study, we found that serum concentrations of IL-10 were significantly increased in SP by using protein array screening. We further determined that the frequency of IL-10-producing CD1dhiCD5+ Bregs, not IL-10-producing non-B lymphocytes, was significantly higher in SP compared to subjects under surveillance (SS) and healthy workers (HW) by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in SP. Th1 cytokines (IFN-γ, IL-2, and IL-12) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were not significantly different between SP, SS, and HW. Our study indicated that IL-10-producing CD1dhiCD5+ Bregs might maintain Tregs and regulate Th1/Th2 polarization in SP, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in SP.

  1. A Common Variant of IL-6R is Associated with Elevated IL-6 Pathway Activity in Alzheimer's Disease Brains.

    Science.gov (United States)

    Haddick, Patrick C G; Larson, Jessica L; Rathore, Nisha; Bhangale, Tushar R; Phung, Qui T; Srinivasan, Karpagam; Hansen, David V; Lill, Jennie R; Pericak-Vance, Margaret A; Haines, Jonathan; Farrer, Lindsay A; Kauwe, John S; Schellenberg, Gerard D; Cruchaga, Carlos; Goate, Alison M; Behrens, Timothy W; Watts, Ryan J; Graham, Robert R; Kaminker, Joshua S; van der Brug, Marcel

    2017-01-01

    The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner. We conducted a screen to identify variants associated with the age of onset of Alzheimer's disease in APOE ɛ4 carriers. Across five datasets, p.D358A had a meta P = 3 ×10-4 and an odds ratio = 1.3, 95% confidence interval 1.12 -1.48. Our study suggests that a common coding region variant of the IL-6 receptor results in neuroinflammatory changes that may influence the age of onset of Alzheimer's disease in APOE ɛ4 carriers.

  2. HBV replication is significantly reduced by IL-6

    Directory of Open Access Journals (Sweden)

    Jeng King-Song

    2009-04-01

    Full Text Available Abstract Interleukin-6 (IL-6 is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.

  3. IL-10: A Multifunctional Cytokine in Viral Infections

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    José M. Rojas

    2017-01-01

    Full Text Available The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.

  4. Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

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    Daisuke Sakurai

    Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

  5. Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

    Directory of Open Access Journals (Sweden)

    Daisuke Sakurai

    Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

  6. Magnetic resonance imaging determined visceral fat reduction associates with enhanced IL-10 plasma levels in calorie restricted obese subjects.

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    Gloria Formoso

    Full Text Available BACKGROUND: Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI protocol before and after weight loss. MATERIALS AND METHODS: In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight. RESULTS: Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05, increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03, and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively. A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05 and IL-6 (r = 0.19 p<0.05 plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels. CONCLUSION: The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

  7. An IL-6 link between obesity and cancer.

    Science.gov (United States)

    Ghosh, Sagar; Ashcraft, Keith

    2013-01-01

    Obesity is a growing epidemic all over the world that by virtue of inducation of a chronic, low-grade, and systemic inflammation leads to an increased risk of a number of diseases, including cancer. IL-6 an important cytokine in the increased risk to cancer in obese patients mainly because of its pro-inflammatory activity. Some data suggest that IL-6 might increase the risk of certain cancers such as those that originate from breast, liver, prostate, colon, and esophagus. A better understanding of the regulation and role of IL-6 in obesity-associated cancer is required to develop effective therapeutic approaches.

  8. Acute stress induces increases in salivary IL-10 levels.

    Science.gov (United States)

    Szabo, Yvette Z; Newton, Tamara L; Miller, James J; Lyle, Keith B; Fernandez-Botran, Rafael

    2016-09-01

    The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1β, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1β/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.

  9. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    Science.gov (United States)

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS.

  10. Preoperative, high IL-6 blood level is a risk factor of postoperative delirium onset in old patients

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    Miriam eCapri

    2014-10-01

    Full Text Available Background: Postoperative delirium (POD is a common complication in elderly patients undergoing surgery, but the underpinning causes are not clear. We hypothesized that inflammaging, the subclinical low and chronic grade inflammation characteristic of old people, can contribute to POD onset. Accordingly, we investigated the association of preoperative and circulating cytokines in elderly patients (>65 yrs, admitted for elective and emergence surgery.Methods: This is secondary analysis of a sub-cohort of patients belonging to a previous large case-control study, where 351 patients were clinically and cognitively thoroughly characterized, together with the assessment of POD (47 patients by Confusion Assessment Method (CAM and Delirium Rating Scale (DRS. 74 preoperative plasma samples were selected from a larger bio-bank and they included 37 subjects with POD and 37 without POD. Inflammaging related cytokines, i.e. IL-1 β, IL-2, IL-6, IL-8, IL-10 and TNF-α were assayed by ELISA in pre-operative blood samples; univariate and multivariable analyses have been applied to identify cytokines independently associated to POD. Associations of cytokine levels with functional status, cognitive decline, intra-hospital mortality and comorbidity were also analyzed independently of POD onset.Results:. High IL-6 and low IL-2 levels were significantly associated with POD. After adjustment for potential confounders in multivariate analysis, high level of preoperative IL-6 was confirmed to be significantly associated with risk of POD onset.. High level of IL-6 was also associated with several baseline features (including poor functional status, cognitive impairment, emergency admission and higher comorbidity burden and intra-hospital mortality.Conclusions: Preoperative, high plasma level of IL-6 ( ≥ 9 pg/mL was significantly associated with POD onset. We propose IL-6 as an additional risk factor of POD onset together with the previously identified factors

  11. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels;

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  12. Determinants of IL-6 levels during HIV infection

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    Álvaro H Borges

    2014-11-01

    Full Text Available Introduction: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD, cancer and death. Compared to the general population, treated HIV+ persons have 50–100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist. Material and Methods: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT with IL-6 plasma levels measured at baseline were included (N=9864. Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates corresponding to fold differences (FDs in IL-6 were calculated. Demographics (age, gender, race, BMI and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different ART regimens were investigated in all three trials. In SMART (N=4498, smoking, comorbidities (CVD, diabetes, hepatitis B/C [HBV/HCV], HDL-cholesterol, renal function (eGFR and educational level were also assessed. Results: Demographics associated with higher IL-6 were older age (FD [95% CI]: 1.09 [1.08–1.11] per 10 yr and higher BMI (1.02 [1.01–1.04] per 5 kg/m2, whereas black race was associated with reduced IL-6 (0.96 [0.93–0.99]. As for HIV variables, patients not receiving ART (1.36 [1.29–1.43] and with higher HIV-RNA (1.24 [1.01–1.52] for >100,000 vs. ≤500 copies/mL had increased IL-6. Participants taking protease inhibitors (PI had higher IL-6 (1.14[1.09–1.19]. Higher nadir CD4 count (0.98 [0.97–0.99]/100 cells/µL was related to lower IL-6. All evaluated comorbidities were related to higher IL-6; FDs in IL-6 were 1.08 [1.04–1.12] for smoking, 1.12 [1.02–1.24] for CVD, 1.07 [1.00–1.16] for diabetes and 1.12 [1.02–1.24] for HBV (1.15 [1.02–1.30] and 1.53 [1.45–1.62] for HCV. IL-6 increased with decreasing eGFR (0.98 [0.97–1.00]/10 mL/min and HDL-cholesterol (0.98 [0.96–0.99]/10 mg/mL. Lower education was related to higher IL-6 (1.09 [1

  13. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  14. The Pathological and Physiological Roles of IL-6 Amplifier Activation

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    Masaaki Murakami, Toshio Hirano

    2012-01-01

    Full Text Available The NFκB-triggered positive feedback loop for IL-6 signaling in type 1 collagen+ non-immune cells (IL-6 amplifier was first discovered to be a synergistic signal that is activated following IL-17A and IL-6 stimulation in type 1 collagen+ non-immune cells. Subsequent disease models have shown that it can also be stimulated by the simultaneous activation of NFκB and STAT3, functions as a local chemokine inducer, and acts as a mechanism for local inflammation, particularly chronic ones like rheumatoid arthritis and a multiple sclerosis. Moreover, we have recently shown that hyper activation of the IL-6 amplifier via regional neural activation establishes a gateway for immune cells including autoreactive T cells to pass the blood-brain barrier at dorsal vessels in 5th lumbar cord. Here we review how the IL-6 amplifier is activated by neural activation and the physiological relevance of the gateway to the central nervous system. Accumulating evidences continues to suggest that the IL-6 amplifier offers a potential molecular mechanism for the relationship between neural activation and the development of inflammatory diseases, which could establish a new interdisciplinary field that fuses neurology and immunology.

  15. Human Pregnancy-Specific Glycoproteins Function as Immunomodulators In Vitro by Inducing Secretion of IL-10 and IL-6 in Human Monocytes

    Science.gov (United States)

    2000-02-29

    by individual Th subset cytokines (Sher and Coffman, 1992, Seder and Paul , (994). Some Th subset cytokines act as autocrine growth factors and promote...cytokine environment during an immune response directs Th subset development (Seder and Paul , 1994). Thl type T cells develop in the presence ofIL-12...biosynthesis through the raslraf-l /meklmapk pathway. Mol Med I: 93-103. Gerard C, Bruyns C, Marchant A, Abramowicz 0, Vandenabeele P, Delvaux A, Fiers

  16. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections

    NARCIS (Netherlands)

    Stappers, M.H.T.; Thys, Y.; Oosting, M.; Plantinga, T.S.; Ioana, M.; Reimnitz, P.; Mouton, J.W.; Netea, M.G.; Joosten, L.A.B.; Gyssens, I.C.J.

    2014-01-01

    Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytoki

  17. IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection.

    Science.gov (United States)

    Assis, Shirleide; Marques, Cintia Rodrigues; Silva, Thiago Magalhães; Costa, Ryan Santos; Alcantara-Neves, Neuza Maria; Barreto, Mauricio Lima; Barnes, Kathleen Carole; Figueiredo, Camila Alexandrina

    2014-06-01

    Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. © 2014 John Wiley & Sons Ltd.

  18. Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family

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    Hideaki Hasegawa

    2016-11-01

    Full Text Available The interleukin (IL-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they are composed of two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than 6 cytokines, including the tentatively named cytokines IL-Y (p28/p40, IL-12 (p35/p40, IL-23 (p19/p40, IL-27 p28/Epstein-Barr virus-induced protein 3 (EBI3, IL-35 (p35/EBI3, and IL-39 (p19/EBI3. This family of cytokines covers a very broad range of immune responses, including pro-inflammatory responses such as helper T (Th1, Th2, and Th17 to anti-inflammatory responses such as regulatory T (Treg cells and IL-10-producing Treg cells. IL-12 is the first member of this family, and IL-12, IL-23, and IL-27 are mainly produced by activated antigen-presenting cells such as dendritic cells and macrophages. IL-12 plays a critical role in the promotion of Th1 immune responses by inducing interferon-γ production to combat pathogens and malignant tumors. IL-23 induces IL-17 production and is necessary to maintain pathogenic Th17 cells that cause inflammatory and autoimmune diseases. IL-27 was initially reported to play a critical role in promotion of Th1 differentiation; however, subsequent studies revealed that IL-27 has broader stimulatory and inhibitory roles by inducing IL-10-producing Treg cells. IL-35 is produced by forkhead box P3+ Treg cells and activated B cells and has immunosuppressive functions to maintain immune tolerance. The most recently identified cytokine, IL-39, is produced by activated B cells and has pro-inflammatory functions. The cytokine tentatively named IL-Y seems to have anti-inflammatory functions by inhibiting Th1 and Th17 differentiation. In addition, individual cytokine subunits were also shown to have self-standing activities. Thus

  19. Análise da citocina IL-1ß e do polimorfismo do gene IL-1B + 3954 em pacientes com implantes osseointegrados

    OpenAIRE

    Melo, Rafaela Fernanda

    2006-01-01

    O objetivo deste estudo foi avaliar a concentração de interleucina-1 ß (IL-1ß) e o polimorfismo na posição +3954 do gene IL-1B em pacientes com a prótese sobre implante, em função, a pelo menos um ano. Vinte e cinco implantes, clinicamente satisfatórios, foram avaliados, em vinte pacientes saudáveis, sendo doze do gênero feminino e oito masculino. Exame clínico completo foi feito em todos os implantes e em um dente em condição de saúde de cada paciente. Amostra do sítio com maior profundidade...

  20. INFLUENCE OF Breg AND IL-10 UPON HUMORAL IMMUNE RESPONSE

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    M. V. Gavrilova

    2016-01-01

    Full Text Available B regulatory cells (Bregs are shown to downregulate autoimmune and inflammation processes. Their modifying effects depend on IL-10 secretion. A role of Bregs in development of humoral immune response was not investigated. Influence of Bregs and IL-10 upon in vitro response of murine B1 and B2 cells to T-dependent and T-independent antigens was studied in a model system. A water-soluble sheep erythrocyte antigen was used as a T-dependent antigen, whereas LPS was applied as a type 1 T-independent antigen, and polyvinylpirrolidone and alpha(1→3dextran were added as type 2 T-independent antigens. В1and B2 lymphocytes were isolated from, respectively, peritoneal cavity and spleen of CBA mice. The cells were cultured in RPMI1640 medium with 10% of FCS supplemented with appropriate antigens and IL-10. The numbers of antibody- and total Ig-forming cells were determined by ELISPOT method.The erythrocyte antigen induced an increase of antibody- and total Ig-forming cell numbers in cultured B1 and B2 cell populations. IL-10 addition caused reduction of antibody- and total Ig-forming cells by 27%. Similarly, IL-10 caused a drop in antibody- and total Ig-forming cells in LPS-stimulated B2 cell cultures by 75%, as well as 50 per cent decrease in numbers of antibody-forming cells in B-1 cell cultures when induced by the type 2 T-independent antigens.To assess functional activity of Bregs, the cells were isolated from peritoneal cavity and spleen of CBA mice. Total yields of Bregs were 20-fold increased upon activation of B cells with LPS, ionomycin and phorbol ester (from 4% to 96%. IgM was the main immunoglobulin isotype secreted by the Bregs. 96% of activated Bregs produced IL-10. About 12% of the cells were shown to produce immunoglobulins. This finding suggests that some of Bregs synthesize both IL-10 and immunoglobulins.To study distant effect of Bregs upon immune response, the splenocyte culture of xid CBA/N mice were tested in Transwells with

  1. Administration of human umbilical cord blood cells produces interleukin-10 (IL-10) in IL-10 deficient mice without immunosuppression.

    Science.gov (United States)

    McCarthy, Brian A; Reddi, Alluru S; Coakley, Kathleen M; Nguyen, Steven M; Nayal, Rasha R; Javdan, Mohammad; Paul, Santanu; Ende, Norman

    2010-03-01

    Recent studies from our laboratory have shown that intravenous administration of human umbilical cord blood (HUCB) mononuclear cells to mice improved blood glucose levels, survival, atherosclerosis and prostate cancer. In this study, we examined the effect of HUCB cells on the production of IL-10 levels in IL-10 knockout mice. It has been proposed that administration of IL-10 may be beneficial in the treatment of inflammatory bowl disease. The results show that mice treated with HUCB cells (100 x 10(6)) produce IL-10, as demonstrated by both qualitative and quantitative analyses, and that the levels of this cytokine persisted until the mice were sacrificed (5.5 months after administration). Immunohistochemical staining of the intestine using HuNu antibody cocktail demonstrated the presence of HUCB cells in the knockout mouse. Although the mice did not receive any immunosuppression, there was no evidence of graft-versus-host disease. Our data suggest that HUCB cells are capable of producing IL-10, and the use of these cells or HUCB may be indicated in the treatment of certain human diseases.

  2. IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system.

    Science.gov (United States)

    Hashizume, Misato; Hayakawa, Naohiko; Suzuki, Miho; Mihara, Masahiko

    2009-10-01

    Angiogenesis in synovia is a characteristic of RA patients. We examined whether IL-6 or TNF-alpha induce tubule formation in a co-culture system of fibroblast-like synovial cells from RA patients (RA-FLS) and human umbilical vein endothelial cells (HUVEC). The effects of IL-6 and TNF-alpha on the expression of angiogenic factors in RA-FLS and HUVEC, and the proliferation of HUVEC were also studied. IL-6 + sIL-6R induced tubule formation, whereas IL-6 alone did not. IL-6/sIL-6R-induced tubule formation was completely suppressed by the addition of either anti-IL-6R or anti-VEGF antibody. TNF-alpha did not induce tubule formation. On the contrary, it decreased CD31-positive area compared with the control. IL-6 + sIL-6R augmented VEGF production in RA-FLS, whereas IL-6 alone did not. Anti-IL-6R antibody suppressed IL-6/sIL-6R-induced VEGF production, but not spontaneous VEGF production. In contrast, TNF-alpha did not induce VEGF production from RA-FLS and HUVEC. IL-6 + sIL-6R stimulation of RA-FLS strongly induced mRNA expression of VEGF, but not of other angiogenic factors, such as EGF, bFGF, TGF-beta, IL-1, TNF-alpha and IL-8. Neither IL-6 nor IL-6/sIL-6R promoted HUVEC proliferation, whereas TNF-alpha significantly inhibited VEGF-induced HUVEC proliferation. In conclusion, IL-6/sIL-6R complex showed angiogenic activity via the production of VEGF from RA-FLS, but TNF-alpha was anti-angiogenic in our experimental system.

  3. IL-6 RESPONSES TO GLYCAEMIC INDEX DURING RECOVERY FROM EXERCISE

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    Hasani S.H.

    2015-06-01

    Full Text Available Purpose: This study examined the effect of meal with different glycaemic index (GI on plasma IL-6 concentration and glucose metabolism after maximal lengthening contractions of the knee extensors. Using a cross-over design, Material : 10 healthy males completed 5 sets of 10 lengthening (eccentric contractions at 120% 1 repetition-maximum. Subjects were randomized to consume the GI beverage (high-GI, low-GI (15% weight per volume; 3 g/kg BM or placebo in three times within 10 min following exercise, and again at 50 and 110 min during recovery time. Blood samples were collected before exercise and after 0.60, 180 min and 24 h of recovery. Results: Concentration of plasma IL-6 in HGI group was less than LGI and Pla groups. IL-6 tended to significantly increase after exercise in recovery time in 3 groups (all P < 0.05, except for 24 hours (P = 1.00, furthermore there was significant difference for IL-6 between placebo and high glycemic groups in 3hours after exercise (P=.016. Concentration of serum CK in HGI group was less than LGI and Pla groups, CK was significantly elevated at all times points during recovery in 3 groups (all P < 0.05, except for 1 hour after exercise in HGI group (P = 0.31, but there was no significant difference for CK between groups. Conclusion: In summary, consuming HGI carbohydrate during recovery from exercise attenuate plasma IL-6 concentration.

  4. The social environment and IL-6 in rats and humans.

    Science.gov (United States)

    Saxton, Katherine B; John-Henderson, Neha; Reid, Matthew W; Francis, Darlene D

    2011-11-01

    Inflammatory cytokine levels predict a wide range of human diseases including depression, cardiovascular disease, type 2 diabetes, autoimmune disease, general morbidity, and mortality. Stress and social experiences throughout the lifecourse have been associated with inflammatory processes. We conducted studies in humans and laboratory rats to examine the effect of early life experience and adult social position in predicting IL-6 levels. Human participants reported family homeownership during their childhood and current subjective social status. Interleukin-6 (IL-6) was measured from oral mucosal transudate. Rats were housed in groups of three, matched for quality of maternal care received. Social status was assessed via competition for resources, and plasma IL-6 was assessed in adulthood. In both humans and rats, we identified an interaction effect; early social experience moderated the effect of adult social status on IL-6 levels. Rats that experienced low levels of maternal care and people with low childhood socioeconomic status represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. The predicted interaction held for non-Hispanic people, but did not occur among Hispanic individuals. Adversity early in life may not have a monotonically negative effect on adult health, but may alter biological sensitivity to later social experiences.

  5. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state?

    Science.gov (United States)

    Giannoudis, Peter V; Harwood, Paul John; Loughenbury, Peter; Van Griensven, Martijn; Krettek, Christian; Pape, Hans-Christoph

    2008-09-01

    Recently, increasing emphasis is being placed upon assessment of the inflammatory status of the patient. Serum inflammatory cytokines, particularly IL-6, have been used as an adjunct to this assessment. Another method uses a combination of simple laboratory and clinical data to provide an assessment of the patient's current level of systemic inflammation, the SIRS. The aim of this study was to investigate, in a group of adult trauma patients, the relationship between the interleukin-6 (IL-6) concentration, the systemic inflammatory response score (SIRS) and outcome. In patients with femoral shaft fracture, serum IL-6 levels and clinical parameters were recorded prospectively on admission and on days 1, 3, 5, and 7. Clinical course, the SIRS score and complications were documented. Nonparametric tests were used to assess relationships between variables and receiver operator characteristic (ROC) curves were used to examine their predictive values. Significance was assumed at the p SIRS state" detected early (day 1 and 3) positively correlated with the IL-6 measurement from the same period (p SIRS state (p SIRS state with an 83% sensitivity and a 75% specificity (area under ROC curve 0.76, p SIRS state and an IL-6 > 300 pg/mL was associated with a significantly increased risk of complication (pneumonia, MOF, death). Both systems were found to be significantly diagnostic of these complications using ROC curve analysis. The IL-6 concentration and SIRS score are useful adjuncts to clinical evaluation of the injured patient. In the early phase, they are closely correlated with the NISS and each other. A cutoff value of 200 pg/dL was shown to be significantly diagnostic of a SIRS state. Significant correlations between adverse events and both the IL-6 level and SIRS state are demonstrated.

  6. Exploitation of Interleukin-10 (IL-10) Signaling Pathways: Alternate Roles of Viral and Cellular IL-10 in Rhesus Cytomegalovirus Infection.

    Science.gov (United States)

    Eberhardt, Meghan K; Deshpande, Ashlesha; Fike, Joseph; Short, Rebecca; Schmidt, Kimberli A; Blozis, Shelley A; Walter, Mark R; Barry, Peter A

    2016-11-01

    There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV and RhCMV, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. In particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vIL-10 suppresses multiple effector functions including, notably, those that link innate and adaptive immune responses. Further, vaccination of RhCMV-uninfected rhesus macaques with nonfunctional forms of RhCMV vIL-10 greatly restricted parameters of RhCMV infection following RhCMV challenge of the vaccinees. Vaccinees exhibited significantly reduced shedding of RhCMV in saliva and urine following RhCMV challenge compared to shedding in unvaccinated controls. Based on the evidence that vIL-10 is critical during acute infection, the role of vIL-10 during persistent infection was analyzed in rhesus macaques infected long term with RhCMV to determine whether postinfection vaccination against vIL-10 could change the virus-host balance. RhCMV-seropositive macaques, which shed RhCMV in saliva, were vaccinated with nonfunctional RhCMV vIL-10, and shedding levels of RhCMV in saliva were evaluated. Following robust increases in vIL-10-binding and vIL-10-neutralizing antibodies, shedding levels of RhCMV modestly declined, consistent with the interpretation that vIL-10 may play a functional role during persistent infection. However, a more significant association was observed between the levels of cellular IL-10 secreted in peripheral blood mononuclear cells exposed to RhCMV antigens and shedding of RhCMV in saliva. This result implies that RhCMV persistence is associated with the induction of cellular IL-10 receptor-mediated signaling pathways. Human health is adversely impacted by viruses that establish lifelong

  7. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    . Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  8. Genetic and bibliographic information: IL10RB [GenLibi

    Lifescience Database Archive (English)

    Full Text Available IL10RB interleukin 10 receptor, beta human Periodontitis (MeSH) Stomatognathic Dise...ases (C07) > Mouth Diseases (C07.465) > Periodontal Diseases (C07.465.714) > Periodontitis (C07.465.714.533) 02A0614091 ...

  9. Filaria-induced IL-10 suppresses murine cerebral malaria.

    Science.gov (United States)

    Specht, Sabine; Ruiz, Daniel Fernández; Dubben, Bettina; Deininger, Susanne; Hoerauf, Achim

    2010-08-01

    Filarial nematodes achieve long survival in their hosts due to their capacity to modulate immune responses. Therefore, immunomodulation by filarial nematodes may alter responses to concomitant infections such as malaria. Cerebral malaria (CM), a severe complication of Plasmodium falciparum infections, is triggered as a consequence of the immune response developed against malaria parasites. The question arises whether prior infection with helminth parasites is beneficial against CM. In the present work a murine model for subsequent has been used to assess this hypothesis. C57BL/6 mice were infected with the rodent filarial parasite Litomosoides sigmodontis and the murine model parasite for CM, Plasmodium berghei ANKA. Previously filaria-infected C57BL/6 mice showed significantly reduced CM rates. CD8(+) T cell recruitment to the brain, a hallmark for CM development, was reduced in protected mice. Furthermore, in contrast to P. berghei single-infected animals, filaria-infected mice had significantly higher levels of circulating IL-10. The requirement for IL-10 in CM protection was demonstrated by the lack of protection in IL-10 KO mice. This suggests that the anti-inflammatory IL-10 elicited by filarial nematodes is able to suppress the overwhelming inflammatory reaction otherwise triggered against malaria parasites in C57BL/6 mice, preventing full progress to CM.

  10. Significant roles played by IL-10 in Chlamydia infections.

    Science.gov (United States)

    Hakimi, Hamid; Zare-Bidaki, Mohammad; Zainodini, Nahid; Assar, Shokrollah; Arababadi, Mohammad Kazemi

    2014-06-01

    Chlamydia species are obligate intracellular parasites which cause usually asymptomatic genital tract infections and also are associated with several complications. Previous studies demonstrated that immune responses to Chlamydia species are different and the diseases will be limited to some cases. Additionally, Chlamydia species are able to modulate immune responses via regulating expression of some immune system molecules including cytokines. IL-10, as the main anti-inflammatory cytokine, plays important roles in the induction of immune-tolerance against self-antigen and also immune-homeostasis after microbe elimination. Furthermore, it has been documented that ectopic expression of IL-10 is associated with several chronic infectious diseases. Therefore, it can be hypothesized that changes in the regulation of this cytokine can be associated with infection with several species of Chlamydia and their associated complications. This review collected the recent information regarding the association and relationship of IL-10 with Chlamydia infections. Another aim of this review article is to address recent data regarding the association of genetic variations (polymorphisms) of IL-10 and Chlamydia infections.

  11. Polymorphisms in the IFNγ, IL-10, and TGFβ Genes May Be Associated with HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Felipe Bonfim Freitas

    2015-01-01

    Full Text Available Objective. This study investigated possible associations between the TNFα-308G/A, IFN+874A/T, IL-6-174C/G, IL-10-1082A/G, and TGFβ-509C/T polymorphisms with HIV-1 infection, in addition to correlation of the polymorphisms with clinical markers of AIDS progression, such as levels of CD4+/CD8+ T lymphocytes and plasma viral load. Methods. A total of 216 individuals who were infected with HIV-1 and on antiretroviral therapy (ART and 294 individuals from the uninfected control group were analyzed. Results. All individuals evaluated were negative for total anti-HBc, anti-HCV, anti-T. pallidum, and anti-HTLV-1/2. The polymorphisms were identified by PCR-RFLP. Individuals presenting the IFN+874A allele as well as the AA genotype were more frequent in the HIV-1 infected group compared to the control group (P<0.05, in addition to having lower levels of CD4+ T lymphocytes. The CD8+ T lymphocytes count was significantly lower in individuals with the IL-10-1082 GG genotype. The TGFβ-509TT genotype was associated with higher plasma viral load. Conclusions. The results suggest that the presence of the IFN+874A allele confers susceptibility to HIV-1 infection and a decrease in the number of CD4+ T lymphocytes. In addition, the genotype associated with high serum levels of TGFβ may be associated with an increase in plasma viral load.

  12. Pathway focused protein profiling indicates differential function for IL-1B, -18 and VEGF during initiation and resolution of lung inflammation evoked by carbon nanoparticle exposure in mice

    Directory of Open Access Journals (Sweden)

    Hamelmann Eckard

    2009-12-01

    Full Text Available Abstract Background Carbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. Pulmonary inflammation caused by deposited nanoparticles is central for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. Therefore we selected a mouse strain C3H/HeJ (C3 with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP to study the elicited pulmonary inflammation and its resolution. Methods 5 μg, 20 μg and 50 μg CNP were intratracheally (i.t. instilled in C3 mice to identify the optimal dose for subsequent time course studies. Pulmonary inflammation was assessed using histology, bronchoalveolar lavage (BAL analysis and by a panel of 62 protein markers. Results 1 day after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5 μg representing the 'no effect level' as reflected by polymorphonuclear leucocyte (PMN, and BAL/lung concentrations of pro-inflammatory proteins. Histological analysis and BAL-protein concentration did not reveal any evidence of tissue injury in 20 μg CNP instilled animals. Accordingly time course assessment of the inflammatory response was performed after 3 and 7 days with this dose (20 μg. Compared to day 1, BAL PMN counts were significantly decreased at day 3 and completely returned to normal by day 7. We have identified protein markers related to the acute response and also to the time dependent response in lung and BAL. After complete resolution of PMN influx on day 7, we detected elevated concentrations of 20 markers that included IL1B, IL18, FGF2, EDN1, and VEGF in lung and/or BAL. Biological pathway analysis revealed these factors to be involved in a

  13. Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion.

    Science.gov (United States)

    Zhu, Liqiong; Chen, Hui; Liu, Meilan; Yuan, Yu; Wang, Zhaohua; Chen, Ying; Wei, Jing; Su, Fang; Zhang, Jianping

    2016-10-02

    Regulatory T cells (Treg) and T helper 17 cells (Th17) are 2 distinct subsets of CD4(+) T cells, which are mutually antagonistic in the immune response. Recently, dysregulation of these 2 cell subsets have been described in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The purpose of this study was to investigate whether the Treg/Th17 balance was perturbed in URSA patients and to explore contributing factors. We found that the proportion of Treg cells and expression of forkhead box P3 (Foxp3) messenger RNA (mRNA) were significantly lower in URSA patients than in healthy controls. However, the proportion of Th17 cells and expression of retinoid-related orphan nuclear receptor-γt (ROR-γt) mRNA were higher in URSA patients than in controls, revealing inverse correlation with Treg. The ratio of Treg/Th17 and Foxp3/ROR-γt decreased in patients with URSA compared to healthy controls. The serum levels of interleukin (IL)-6 and IL-17A were significantly higher, whereas IL-10 was lower in URSA patients compared with controls, and the level of IL-6 showed a positive correlation with Th17, ROR-γt and inverse correlation with Treg, Foxp3. The present study indicated that an imbalance between Treg and Th17 cells might be implicated in the pathogenesis of URSA and this seems to relate to elevation in serum IL-6 level.

  14. IL-10-Producing Type 1 Regulatory T Cells and Allergy

    Institute of Scientific and Technical Information of China (English)

    Kui Wu; Yutian Bi; Kun Sun; Changzheng Wang

    2007-01-01

    As an important subset of regulatory T (Treg) cells, IL-10-producing type 1 regulatory T cells (Tr1), have some different features to thymic-derived naturally occurring CD4+CD25+Foxp3+ Treg cells(nTreg cells). Similar to nTreg cells, Tr1 also play important roles in the control of allergic inflammation in several ways. There is a fine balance between Tr1 and Th2 responses in healthy subjects. Skewing of allergic-specific effctor T cells to a Tr1 phenotype appears to be a critical event in successful allergen-specific immunotherapy and glucocorticoids and β2-agonists treatment. Tr1 suppress Th2 cells and effector cells of allergic inflammation, such as eosinophils, mast cells, basophils, through producing IL-10, and perhaps TGF-β. Understanding of Tr1 may be helpful in developing new strategies for treatment of allergic diseases.

  15. The paradoxical role of IL-10 in immunity and cancer.

    Science.gov (United States)

    Mannino, Mark H; Zhu, Ziwen; Xiao, Huaping; Bai, Qian; Wakefield, Mark R; Fang, Yujiang

    2015-10-28

    Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated. In this review, we will discuss a wide variety of evidence of IL-10 in immunity and cancer in an effort to illuminate the remaining mysteries in the function of this cytokine that, when fully understood, may prove to be a powerful tool in the battle against cancer.

  16. Increased Pro-inflammatory Cytokines (TNF-a and IL-6 and Anti-inflammatory Compounds (sTNFRp55 and sTNFRp75 in Brazilian Patients during Exanthematic Dengue Fever

    Directory of Open Access Journals (Sweden)

    Luzia MO Pinto

    1999-05-01

    Full Text Available Pro-inflammatory cytokines, tumor necrosis factor (TNF-a, interleukin-6 (IL-6 and interleukin-1b (IL-1b as well as anti-inflammatory compounds, soluble TNF-Receptor p55 (sTNFRp55, sTNFRp75 and IL-1 receptor antagonist (sIL-1Ra, were investigated in 34 Brazilian cases of dengue fever (DF originated from a study of exanthematic virosis. The presence of pro-inflammatory cytokines was detected in sera from these patients by ELISA. TNF-a and IL-6 levels were significantly higher than control subjects in 32% and 52% patients, respectively. To our knowledge this was the first time a receptor antagonist and soluble receptors for cytokines were detected in sera obtained during exanthematic DF without hemorrhagic manifestations. Both sTNFRp55 and sTNFRp75 were consistently elevated in 42% and 84% patients, respectively. Most patients had IL-1b levels not different from those of normal subjects, except for one case. Only 16% patients had altered levels of IL-1Ra. Previous studies in dengue hemorrhagic fever patients demonstrated production of these soluble factors; here we observed that they are found in absence of hemorrhagic manifestations. The possible role of these anti-inflammatory compounds in immune cell activation and in regulating cytokine-mediated pathogenesis during dengue infection is discussed.

  17. ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro.

    Science.gov (United States)

    Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Huijie; Yuan, Yuan; Ji, Zhenyu; Qiao, Baoping; Wen, Jian-Guo; Zhang, Mingzhi; Kvalheim, Gunnar; Nesland, Jahn M; Suo, Zhenhe

    2015-12-15

    Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2'-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells.

  18. 白细胞介素-10选择性抑制钛颗粒激活的巨噬细胞活性研究%IL-10 selectively inhibiting the activity of macrophage stimulated by titanium particles

    Institute of Scientific and Technical Information of China (English)

    王毅; 何川; 杨庆铭; 邓廉夫; Sturad Goodman

    2004-01-01

    目的本实验研究钛颗粒通过特定的信号传递通道激活巨噬细胞的转录因子核因子-IL-6(NF-IL-6)、核因子-κB(NF-κB)的表达,检测白细胞介素(IL)-1β、-6和肿瘤坏死因子(TNF)-α水平,并采用细胞因子抑制剂IL-10处理巨噬细胞,观察其对巨噬细胞活性的抑制作用.方法从健康人外周静脉血中分离单核/巨噬细胞,进行体外培养.巨噬细胞处理用钛颗粒浓度为 0.075% (体积比).IL-10组先用IL-10(20μg/L)预处理巨噬细胞10min,后再加入钛颗粒.按不同时间段采集细胞培养液和巨噬细胞.培养液中细胞因子IL-6、IL-1β和TNF-α采用ELISA方法检测.巨噬细胞经核酸抽提,采用EMSA方法检测NF-IL-6和NF-κB,并经半定量分析.结果未经钛颗粒刺激的巨噬细胞,48h内上清液中未能检测出上述细胞因子.钛颗粒刺激后2h,上清液中检测出IL-6,4h后可检测出IL-1β和TNF-α.TNF-α在12h达到高峰,IL-6和IL-1β在24h达到高峰,随后下降.IL-10在各时相抑制近一半IL-6的释放 (P 0.05). 经钛颗粒刺激后1h,EMSA方法即可检测出NF-IL-6表达,并持续表达5h.IL-10预处理的巨噬细胞,NF-IL-6的表达量减少 (P 0.05).结论钛颗粒能够激活巨噬细胞合成和释放细胞因子IL-6、IL-1β和TNF-α.IL-10抑制NF-IL-6的表达,从而抑制IL-6的合成和释放,为解决假体周围骨溶解问题,提供一种新的可能.IL-1选择性抑制NF-IL-6,说明巨噬细胞对不同的刺激,存在有不同的信号传递途径.

  19. Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

    Directory of Open Access Journals (Sweden)

    Joonhee Cho

    Full Text Available BACKGROUND AND AIMS: Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI. METHODS: To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function. RESULTS: BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6. CONCLUSIONS: 17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a

  20. Genetic and bibliographic information: IL6ST [GenLibi

    Lifescience Database Archive (English)

    Full Text Available IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor) human Periodontitis...iodontal Diseases (C07.465.714) > Periodontitis (C07.465.714.533) Stomatognathic Diseases (C07) > Mouth Dise...ases (C07.465) > Periodontal Diseases (C07.465.714) > Periodontitis (C07.465.714.533) > Aggressive Periodontitis (C07.465.714.533.161) 04A0389761 ...

  1. A workflow for in silico design of hIL-10 and ebvIL-10 inhibitors using well-known miniprotein scaffolds.

    Science.gov (United States)

    Dueñas, Salvador; Aguila, Sergio A; Pimienta, Genaro

    2017-04-01

    The over-expression of immune-suppressors such as IL-10 is a crucial landmark in both tumor progression, and latent viral and parasite infection. IL-10 is a multifunctional protein. Besides its immune-cell suppressive function, it also promotes B-cell tumorigenesis of lymphomas and melanoma. Human pathogens like unicellular parasites and viruses that remain latent inside B cells promote the over-expression of hIL-10 upon infection, which inhibits cell-mediated immune surveillance, and at the same time mediates B cell proliferation. The B-cell specific oncogenic latent virus Epstein-Barr virus (EBV) encodes a viral homologue of hIL-10 (ebvIL-10), expressed during lytic viral proliferation. Once expressed, ebvIL-10 inhibits cell-mediated immune surveillance, assuring EBV re-infection. During long-term latency, EBV-infected B cells over-express hIL-10 to assure B-cell proliferation, occasionally inducing EBV-mediated lymphomas. The amino acid sequences of hIL-10 and ebvIL-10 are more than 80% identical and thus have a very similar tridimensional structure. Based on their published crystallographic structures bound to their human receptor IL10R1, we report a structure-based design of hIL-10 and ebvIL-10 inhibitors based on 3 loops from IL10R1 that establish specific hydrogen bonds with the two IL10s. We have grafted these loops onto a permissible loop in three well-known miniprotein scaffolds-the Conus snail toxin MVIIA, the plant-derived trypsin inhibitor EETI, and the human appetite modulator AgRP. Our computational workflow described in detail below was invigorated by the negative and positive controls implemented, and therefore paves the way for future in vitro and in vivo validation assays of the IL-10 inhibitors engineered.

  2. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    Science.gov (United States)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  3. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

    Science.gov (United States)

    Shearer, W. T.; Reuben, J. M.; Mullington, J. M.; Price, N. J.; Lee, B. N.; Smith, E. O.; Szuba, M. P.; Van Dongen, H. P.; Dinges, D. F.

    2001-01-01

    BACKGROUND: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. OBJECTIVE: We sought to measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-alpha receptor (sTNF-alpha R) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. METHODS: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-alpha RI, sTNF-alpha RII, IL-6, soluble IL-2 receptor, IL-10, and TNF-alpha. RESULTS: Interactions between the effects of time and sleep deprivation level were detected for sTNF-alpha RI and IL-6 but not for sTNF-alpha RII, soluble IL-2 receptor, IL-10, and TNF-alpha. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-alpha RI on day 2 (P =.04), day 3 (P =.01), and across days 2 to 4 of sleep loss (P =.01) and elevated levels of IL-6 on day 4 (P =.04). CONCLUSIONS: Total sleep loss produced significant increases in plasma levels of sTNF-alpha RI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight.

  4. DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

    Institute of Scientific and Technical Information of China (English)

    Fan Wanhu; Chen Ruilin; Yue Jinsheng; Liu Zhengwen; Zhang Shulin

    2006-01-01

    Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

  5. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    DEFF Research Database (Denmark)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the ...

  6. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    DEFF Research Database (Denmark)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan;

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the ...

  7. Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging.

    NARCIS (Netherlands)

    Hooge, A.S.K. de; Loo, F.A.J. van de; Bennink, M.B.; Arntz, O.J.; Hooge, P. de; Berg, W.B. van den

    2005-01-01

    OBJECTIVE: Interleukin-6 (IL-6) is expressed in osteoarthritic joints but its function in osteoarthritis (OA) is unknown. To study this, spontaneous and experimental OA were evaluated in IL-6 deficient (IL-6(-/-)) mice. DESIGN: Histology of knees of 18-23-month-old wild type (wt) and IL-6(-/-) mice

  8. IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

    Science.gov (United States)

    Polukort, Stephanie H; Rovatti, Jeffrey; Carlson, Logan; Thompson, Chelsea; Ser-Dolansky, Jennifer; Kinney, Shannon R M; Schneider, Sallie S; Mathias, Clinton B

    2016-06-15

    IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/-) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcεRI expression on mast cells; and enhanced the production of mast cell cytokines. IL-10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms.

  9. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida

    2015-07-01

    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  10. The bioactivity of teleost IL-6: IL-6 protein in orange-spotted grouper (Epinephelus coioides) induces Th2 cell differentiation pathway and antibody production.

    Science.gov (United States)

    Chen, Hsin-Hung; Lin, Han-Tso; Foung, Yi-Fan; Han-You Lin, John

    2012-10-01

    Interleukin 6 (IL-6) is a protein secreted by T cells and macrophages and plays an important role in immune response. IL-6 regulates the proliferation and differentiation of T cells, and elicits immunoglobulin production in B cells. In this study, the cDNA il-6 (gil-6) sequence of the orange spotted grouper (Epinephelus coioides) was obtained. The deduced IL-6 (gIL-6) protein comprised 223 amino acids, the sequence shared approximately 30% similarity with mammalian IL-6, and between 47% and 69% similarity with other available teleost IL-6. The protein comprises the signal peptide, the IL-6 family signature, and conserved amino acid residues found in IL-6 sequences of other teleost. In order to understand the bioactivity and influence of gIL-6 on humoral immune response, recombinant gIL-6 (rgIL-6) synthesized by prokaryotes was injected into orange spotted groupers, and the immune-related gene expression at various times in various organs was observed. Our results revealed that the Th1 specific transcription factor t-bet was down-regulated and Th2 specific transcription factors gata3, and c-maf were up-regulated in immune organs, following IL-6 stimulation. Additionally, higher levels of igm mRNA and translated protein were detected in rgIL-6 stimulated fish. These results indicate that IL-6 in groupers regulates the differentiation of naїve T helper cells into Th2 cells and elicits the production of antibodies.

  11. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    OsamaEl-Assal; FengHong; Won-HoKim; SvetlanaRadaeva; BinGao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however,the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes v/a induction of metallothionein protein expression, which mav account for the nrotective role of IL-6 in alcoholic liver disease.

  12. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    Osama El-Assal; Feng Hong; Won-Ho Kim; Svetlana Radaeva; Bin Gao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes via induction of metallothionein protein expression, which may account for the protective role of IL-6 in alcoholic liver disease.

  13. Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice

    DEFF Research Database (Denmark)

    Gavito, A L; Cabello, R; Suarez, J;

    2016-01-01

    BACKGROUND AND PURPOSE: Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic...... in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells. KEY RESULTS: During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression...... lipogenic enzymes. EXPERIMENTAL APPROACH: Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated...

  14. Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-06-14

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  15. Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-07-19

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  16. Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.

    Science.gov (United States)

    Gavito, A L; Cabello, R; Suarez, J; Serrano, A; Pavón, F J; Vida, M; Romero, M; Pardo, V; Bautista, D; Arrabal, S; Decara, J; Cuesta, A L; Valverde, A M; Rodríguez de Fonseca, F; Baixeras, E

    2016-03-01

    Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic lipogenic enzymes. Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells. During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL-6(-/-) mice. Protein levels of hepatic lipogenic enzymes were lower in IL-6(-/-) than in WT mice at the end of the fasting period. In WT, circulating IL-6 levels paralleled gene expression of hepatic lipogenic enzymes. IL-6 administration in vivo and in vitro showed that IL-6-mediated signalling was associated with the up-regulation of hepatic lipogenic enzyme genes. Moreover, silencing STAT3 in HepG2 cells attenuated IL-6 mediated up-regulation of lipogenic gene transcription levels. IL-6 sustains levels of hepatic lipogenic enzymes during fasting through activation of STAT3. Our findings indicate that clinical use of STAT3-associated signalling cytokines, particularly against steatosis, should be undertaken with caution. © 2016 The British Pharmacological Society.

  17. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.

    Science.gov (United States)

    Saquib, Quaiser; Al-Khedhairy, Abdulaziz A; Ahmad, Javed; Siddiqui, Maqsood A; Dwivedi, Sourabh; Khan, Shams T; Musarrat, Javed

    2013-12-01

    The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe2O4-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 μg/ml of ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48h of ZnFe2O4-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT(2) Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p<0.01) population of ZnFe2O4-NPs (100 μg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe2O4-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe2O4-NPs induced cellular and genetic damage.

  18. Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10(+) phenotype.

    Science.gov (United States)

    Betto, Elena; Usuelli, Vera; Mandelli, Alessandra; Badami, Ester; Sorini, Chiara; Capolla, Sara; Danelli, Luca; Frossi, Barbara; Guarnotta, Carla; Ingrao, Sabrina; Tripodo, Claudio; Pucillo, Carlo; Gri, Giorgia; Falcone, Marika

    2017-05-01

    Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire an IL-10+ phenotype upon interaction with FoxP3+ Treg cells, MCs of NOD mice do not undergo this tolerogenic differentiation. Our data indicate that overly inflammatory MCs unable to acquire a tolerogenic IL-10+ phenotype contribute to the pathogenesis of autoimmune T1D. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Hsp65-Producing Lactococcus lactis Prevents Inflammatory Intestinal Disease in Mice by IL-10- and TLR2-Dependent Pathways

    Science.gov (United States)

    Gomes-Santos, Ana Cristina; de Oliveira, Rafael Pires; Moreira, Thaís Garcias; Castro-Junior, Archimedes Barbosa; Horta, Bernardo Coelho; Lemos, Luísa; de Almeida, Leonardo Augusto; Rezende, Rafael Machado; Cara, Denise Carmona; Oliveira, Sérgio Costa; Azevedo, Vasco Ariston Carvalho; Miyoshi, Anderson; Faria, Ana Maria Caetano

    2017-01-01

    Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria. Using an IBD mouse model, we showed that oral pretreatment with genetically modified Lactococcus lactis that produces and releases Mycobacterium Hsp65, completely prevented DSS-induced colitis in C57BL/6 mice. Protection was associated with reduced pro-inflammatory cytokines, such as IFN-γ, IL-6, and TNF-α; increased IL-10 production in colonic tissue; and expansion of CD4+Foxp3+ and CD4+LAP+ regulatory T cells in spleen and mesenteric lymph nodes. This effect was dependent on IL-10 and toll-like receptor 2. Thus, this approach may open alternative options for long-term management of IBD. PMID:28194152

  20. Family-based association study of interleukin 10 (IL10) and interleukin 10 receptor alpha (IL10RA) functional polymorphisms in schizophrenia in Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2016-08-15

    Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. Interleukin-10 (IL10) and it's receptor IL10RA may play an important role for immunological aspects in etiologies of major psychiatric disorders including schizophrenia. The aim of this study was to perform a transmission disequilibrium test (TDT) on a group of 146 schizophrenia trios from the Polish population. Functional polymorphisms from IL10 (rs1800872, rs1800871, rs1800896, rs1800890, and rs6676671) and IL10RA (rs3135932 and rs2229113) genes were analyzed. A lack of association with schizophrenia was detected for IL10 and IL10RA single polymorphisms and haplotypes. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis.

    Science.gov (United States)

    Yang, Jie; Qian, Shihui; Cai, Xueting; Lu, Wuguang; Hu, Chunping; Sun, Xiaoyan; Yang, Yang; Yu, Qiang; Gao, S Paul; Cao, Peng

    2016-06-01

    The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6-IL6Rα-GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190-200. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Family-based association study of interleukin 6 (IL6) and its receptor (IL6R) functional polymorphisms in schizophrenia in the Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Permoda-Osip, Agnieszka; Twarowska-Hauser, Joanna

    2015-08-15

    Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. Recent studies indicate a role of excessive interleukin-6 (IL6) signaling in the pathogenesis of schizophrenia. Findings regarding changes in the circulating levels of soluble interleukin-6 receptor (sIL6R) in schizophrenia have been equivocal. The study was performed on a group of 147 trio (patients diagnosed with schizophrenia and their healthy parents). Polymorphisms of IL6 (rs1800795, rs1800797) and IL6R (rs4537545, rs4845617, rs2228145) genes were genotyped with the use of TaqMan SNP Genotyping Assays. No association of the polymorphisms from IL6 and IL6R genes with schizophrenia was found. We also investigated haplotypes in IL6 gene (consisting of rs1800795 and rs1800797) and in IL6R gene (consisting of rs4537545, rs2228145). We also found no preference in transmission of any haplotype. Our results do not support the theory that polymorphisms of IL6 and IL6R genes are involved in the pathogenesis of schizophrenia. It seems advisable to carry out further examinations of the role of these polymorphisms in schizophrenia by means of TDT method and classical (case-control) association method.

  3. Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

    Directory of Open Access Journals (Sweden)

    Elisabeth Lippert

    Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

  4. Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Anna M. Fulghesu

    2011-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR and insulin resistant (IR, and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β and lipokines (leptin, adiponectin, the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6 was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

  5. Expression of IL-8, IL-6 and IL-1β in tears as a main characteristic of the immune response in human microbial keratitis.

    Science.gov (United States)

    Santacruz, Concepcion; Linares, Marisela; Garfias, Yonathan; Loustaunau, Luisa M; Pavon, Lenin; Perez-Tapia, Sonia Mayra; Jimenez-Martinez, Maria C

    2015-03-03

    Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4+, CD8+, CD19+ and CD3-CD56+ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 > IL-6 in patients with bacterial keratitis; IL-8 > IL-6 > IL-1β and increased frequency of circulating CD3-CD56+ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 > IL-1β in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans.

  6. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells

    Energy Technology Data Exchange (ETDEWEB)

    Saquib, Quaiser; Al-Khedhairy, Abdulaziz A.; Ahmad, Javed; Siddiqui, Maqsood A.; Dwivedi, Sourabh; Khan, Shams T. [Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh 202002, U.P. (India)

    2013-12-01

    The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe{sub 2}O{sub 4}-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 μg/ml of ZnFe{sub 2}O{sub 4}-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48 h of ZnFe{sub 2}O{sub 4}-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT{sup 2} Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p < 0.01) population of ZnFe{sub 2}O{sub 4}-NPs (100 μg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe{sub 2}O{sub 4}-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe{sub 2}O{sub 4}-NPs induced cellular and genetic damage. - Highlights: • First report on the molecular toxicity of ZnFe{sub 2}O{sub 4}-NPs in cells of placental origin • WISH cells treated with ZnFe{sub 2}O{sub 4}-NPs exhibited cytoplasmic

  7. ROLE OF IL-6 IN EXPERIMENTAL ARTHRITIS CAUSED BY TRANSFER OF ARTHRITOGENIC ANTIBODIES

    Directory of Open Access Journals (Sweden)

    M. S. Drutskaya

    2016-01-01

    Full Text Available Interleukin-6 (IL-6 exerts important functions on immune regulation. In case of high expression, IL-6 may promote autoimmune disorders, e.g., arthritis. Systemic IL-6 blockers based on monoclonal antibodies against IL-6, or its specific receptor subunit, are already used in clinical settings, adding to a range of known biological drugs, such as, TNF blockers. Rheumatic disorders and their experimental therapy are reproducible in mice. This study revealed systemically increased levels of IL-6 in developing arthritis caused by transfer of pathogenic antibodies, as well as the effects of IL-6 neutralization by monoclonal antibodies against murine IL-6. Our results suggest a pathogenic role of the two cytokines, TNF and IL-6, in experimental arthritis induced by passive transfer of anti-collagen antibodies.

  8. Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Brandauer, Josef; Schjerling, Peter

    2013-01-01

    Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse...... muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP-containing vesicles and protein by 62% (P ... and progressively over 25 min of contraction. However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice...

  9. Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Poirier Judes

    2011-10-01

    Full Text Available Abstract Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog in subjects with mild to moderate Alzheimer's disease (AD. Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4 were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805.

  10. Role of the IL-6 Gene in the Etiopathogenesis of Idiopathic Scoliosis

    OpenAIRE

    Svetla Nikolova; Milka Dikova; Dobrin Dikov; Assen Djerov; Gyulnas Dzhebir; Ventseslav Atanasov; Alexey Savov; Ivo Kremensky

    2015-01-01

    Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6). The G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS) and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and the IL-6 promoter polymorphism at -174 p...

  11. LPS-induced release of IL-6 from glia modulates production of IL-1beta in a JAK2-dependent manner

    LENUS (Irish Health Repository)

    Minogue, Aedín M

    2012-06-14

    AbstractBackgroundCompelling evidence has implicated neuroinflammation in the pathogenesis of a number of neurodegenerative conditions. Chronic activation of both astrocytes and microglia leads to excessive secretion of proinflammatory molecules such as TNFα, IL-6 and IL-1β with potentially deleterious consequences for neuronal viability. Many signaling pathways involving the mitogen-activated protein kinases (MAPKs), nuclear factor κB (NFκB) complex and the Janus kinases (JAKs)\\/signal transducers and activators of transcription (STAT)-1 have been implicated in the secretion of proinflammatory cytokines from glia. We sought to identify signaling kinases responsible for cytokine production and to delineate the complex interactions which govern time-related responses to lipopolysaccharide (LPS).MethodsWe examined the time-related changes in certain signaling events and the release of proinflammatory cytokines from LPS-stimulated co-cultures of astrocytes and microglia isolated from neonatal rats.ResultsTNFα was detected in the supernatant approximately 1 to 2 hours after LPS treatment while IL-1β and IL-6 were detected after 2 to 3 and 4 to 6 hours, respectively. Interestingly, activation of NFκB signaling preceded release of all cytokines while phosphorylation of STAT1 was evident only after 2 hours, indicating that activation of JAK\\/STAT may be important in the up-regulation of IL-6 production. Additionally, incubation of glia with TNFα induced both phosphorylation of JAK2 and STAT1 and the interaction of JAK2 with the TNFα receptor (TNFR1). Co-treatment of glia with LPS and recombinant IL-6 protein attenuated the LPS-induced release of both TNFα and IL-1β while potentiating the effect of LPS on suppressor of cytokine signaling (SOCS)3 expression and IL-10 release.ConclusionsThese data indicate that TNFα may regulate IL-6 production through activation of JAK\\/STAT signaling and that the subsequent production of IL-6 may impact on the release of

  12. The effect of repeated endurance exercise on IL-6 and sIL-6R and their relationship with sensations of fatigue at rest.

    Science.gov (United States)

    Robson-Ansley, Paula; Barwood, Martin; Canavan, Jane; Hack, Susan; Eglin, Clare; Davey, Sarah; Hewitt, Jennifer; Hull, James; Ansley, Les

    2009-02-01

    Strenuous, prolonged exercise increases interleukin-6 (IL-6) release. The effect of IL-6 is dependent on the availability of IL-6 receptors. Few studies have addressed the impact of exercise on IL-6 receptor levels or procalcitonin (PCT), an indicator of systemic inflammation. Changes in these molecules may give insight into cytokine-related mechanisms underlying exercise-related fatigue. Thirteen trained male subjects partook in the study. They cycled a total distance of 468 km over 6 days. Blood samples were obtained prior to and immediately following Day 1 of the study and then each morning prior to exercise. Blood samples were analysed for plasma IL-6, soluble IL-6 receptor (sIL-6R), C-reactive protein (CRP), PCT, creatine kinase (CK) and cortisol concentrations. Subjects also completed mood state questionnaires each day prior to exercise. IL-6 was elevated immediately post-exercise on Day 1 but was unchanged at rest for the duration of the event. In contrast, sIL-6R, CRP, PCT and CK concentrations were unchanged immediately post-exercise on Day 1 but were significantly elevated at rest over the duration of the event compared with pre-event baseline. sIL-6R was highly correlated to CRP. Cortisol concentrations remained unchanged at all time points. In conclusion, strenuous, prolonged exercise stimulated an acute phase response which was maintained throughout the 6-day event. sIL-6R increase is associated with CRP and may affect subjective sensations of post-exercise fatigue at rest.

  13. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  14. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.

    Science.gov (United States)

    Ogata, Toshiyuki; Yamazaki, Hideya; Teshima, Teruki; Kihara, Ayaka; Suzumoto, Yuko; Inoue, Takehiro; Nishimoto, Norihiro; Matsuura, Nariaki

    2010-04-07

    Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice. BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  15. Effects of ginkgo biloba extract on the expressions of IL-1β, TNF-α,IL-10 and IL-10R in heart of atherosclerotic rats

    Institute of Scientific and Technical Information of China (English)

    JIAO Ya-bin; RUI Yao-cheng; LI Tie-jun; YANG Peng-yuan; QIU Yan

    2006-01-01

    Objective:To study whether the anti-AS effect of ginkgo biloba extract (GbE) was related with inhibitory effects on the expression of IL-1β, TNF-α and up-regulation of IL-10 and IL-10R in the heart of atherosclerotic (AS)rats. Methods:The experimental model of AS rats were established by intraperitioneal injection of vitamin D3 with high fat and cholesterol diet. All rats were divided into 3 groups: control,AS and GbE. GbE (100 mg/kg) was administered to rats by ig. After 8 weeks, the expression of IL-1β, TNF-α, IL-10, and IL-10R in the heart of AS rats were detected by enzyme-linked immunosorbant assay, reverse transcriptase polymerasechain reaction and Western blotting. Results:The protein and mRNA expressions of IL-1β,TNF-α,IL-10 and IL-10R were markedly higher in AS group than those in control group (P<0.01). The protein and mRNA expressions of IL-1β and TNF-α were markedly lower in GbE group than those in AS group; while the protein and mRNA expressions of IL-10 and IL-10R were markedly higher in GbE group than those in AS group (P<0.01). Conclusion:GbE has significant inhibitory effects on proinflammatory cytokine IL-1β,TNF-α. The up-regulation of anti-inflammatory cytokine IL-10,IL-10R that may be partially responsible for its anti-AS effects.

  16. IL-10 and its related cytokines for treatment of inflammatory bowel disease.

    Science.gov (United States)

    Li, Ming-Cai; He, Shao-Heng

    2004-03-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis are chronic inflammatory disorders of gastrointestinal tract. Although the etiology is incompletely understood, initiation and aggravation of the inflammatory process seem to be due to a massive local mucosal immune response. Interleukin-10 (IL-10) is a regulatory cytokine which inhibits both antigen presentation and subsequent pro-inflammatory cytokine release, and it is proposed as a potent anti-inflammatory biological therapy in chronic IBD. Many methods of IL-10 as a treatment for IBD have been published. The new strategies of IL-10 treatment, including recombinant IL-10, the use of genetically modified bacteria, gelatine microsphere containing IL-10, adenoviral vectors encoding IL-10 and combining regulatory T cells are discussed in this review. The advantages and disadvantages of these IL-10 therapies are summarized. Although most results of recombinant IL-10 therapies are disappointing in clinical testing because of lacking efficacy or side effects, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response. Novel IL-10-related cytokines, including IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29, are involved in regulation of inflammatory and immune responses. The use of IL-10 and IL-10-related cytokines will provide new insights into cell-based and gene-based treatment against IBD in near future.

  17. IL-10 is critical for Th2 responses in a murine model of allergic dermatitis.

    Science.gov (United States)

    Laouini, Dhafer; Alenius, Harri; Bryce, Paul; Oettgen, Hans; Tsitsikov, Erdyni; Geha, Raif S

    2003-10-01

    We found that mechanical injury to mouse skin, which can be caused by tape stripping, results in rapid induction of IL-10 mRNA. IL-10-/- mice were used to examine the role of IL-10 in a mouse model of allergic dermatitis induced by epicutaneous (EC) sensitization with OVA on tape-stripped skin. Skin infiltration by eosinophils and expression of eotaxin, IL-4, and IL-5 mRNA in OVA-sensitized skin sites were severely diminished in IL-10-/- mice. Following in vitro stimulation with OVA, splenocytes from EC-sensitized IL-10-/- mice secreted significantly less IL-4, but significantly more IFN-gamma, than splenocytes from WT controls. A similar skewing in cytokine secretion profile was observed in the splenocytes of IL-10-/- mice immunized intraperitoneally with OVA. IL-10-/- APCs skewed the in vitro response of OVA T cell receptor (TCR) transgenic T cells towards Th1. Examination of the Th response of WT and IL-10-/- mice immunized with OVA-pulsed WT or IL-10-/- DCs revealed that both DCs and T cells participate in IL-10 skewing of the Th2 response in vivo. These results suggest that IL-10 plays an important role in the Th2 response to antigen and in the development of skin eosinophilia in a murine model of allergic dermatitis.

  18. IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes.

    Science.gov (United States)

    Dong, Jun; Ivascu, Claudia; Chang, Hyun-Dong; Wu, Peihua; Angeli, Roberta; Maggi, Laura; Eckhardt, Florian; Tykocinski, Lars; Haefliger, Carolina; Möwes, Beate; Sieper, Jochen; Radbruch, Andreas; Annunziato, Francesco; Thiel, Andreas

    2007-08-15

    Epigenetic modifications, including DNA methylation, profoundly influence gene expression of CD4(+) Th-specific cells thereby shaping memory Th cell function. We demonstrate here a correlation between a lacking fixed potential of human memory Th cells to re-express the immunoregulatory cytokine gene IL10 and its DNA methylation status. Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. Limited difference in methylation was found for the IL10 gene locus in IL-10-secreting Th cells, as compared with Th cells not secreting IL-10 isolated directly ex vivo or from in vitro-established human Th1 and Th2 clones. In contrast, in IFN-gamma(+) memory Th cells the promoter of the IFNG gene was hypomethylated, as compared with IFN-gamma-nonsecreting memory Th cells. In accordance with the lack of epigenetic memory, almost 90% of ex vivo-isolated IL-10-secreting Th cells lacked a functional memory for IL-10 re-expression after restimulation. Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential.

  19. IL-10 and its related cytokines for treatment of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Ming-Cai Li; Shao-Heng He

    2004-01-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis are chronic inflammatory disorders of gastrointestinal tract. Although the etiology is incompletely understood, initiation and aggravation of the inflammatory process seem to be due to a massive local mucosal immune response. Interleukin-10 (IL-10) is a regulatory cytokine which inhibits both antigen presentation and subsequent pro-inflammatory cytokine release, and it is proposed as a potent anti-inflammatory biological therapy in chronic IBD. Many methods of IL-10 as a treatment for IBD have been published. The new strategies of IL-10 treatment, including recombinant IL-10, the use of genetically modified bacteria, gelatine microsphere containing IL-10,adenoviral vectors encoding IL-10 and combining regulatory T cells are discussed in this review. The advantages and disadvantages of these IL-10 therapies are summarized.Although most results of recombinant IL-10 therapies are disappointing in clinical testing because of lacking efficacy or side effects, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response. Novel IL-10-related cytokines, including IL-t9, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29, are involved in regulation of inflammatory and immune responses. The use of IL-10 and IL-10-related cytokines will provide new insights into cell-based and gene-based treatment against IBD in near future.

  20. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.

    Science.gov (United States)

    Zigmond, Ehud; Bernshtein, Biana; Friedlander, Gilgi; Walker, Catherine R; Yona, Simon; Kim, Ki-Wook; Brenner, Ori; Krauthgamer, Rita; Varol, Chen; Müller, Werner; Jung, Steffen

    2014-05-15

    Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome-wide association studies and experimental animal models point at a central role of the IL-10 axis in inflammatory bowel diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10Rα) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1-expressing macrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages and resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning agent in the colon and define intestinal CX3CR1(hi) macrophages as a decisive factor that determines gut health or inflammation.

  1. Surface-Displayed IL-10 by Recombinant Lactobacillus plantarum Reduces Th1 Responses of RAW264.7 Cells Stimulated with Poly(I:C) or LPS.

    Science.gov (United States)

    Cai, Ruopeng; Jiang, Yanlong; Yang, Wei; Yang, Wentao; Shi, Shaohua; Shi, Chunwei; Hu, Jingtao; Gu, Wei; Ye, Liping; Zhou, Fangyu; Gong, Qinglong; Han, Wenyu; Yang, Guilian; Wang, Chunfeng

    2016-02-01

    Recently, poly-γ-glutamic acid synthetase A (pgsA) has been applied to display exogenous proteins on the surface of Lactobacillus casei or Lactococcus lactis, which results in a surfacedisplayed component of bacteria. However, the ability of carrying genes encoded by plasmids and the expression efficiency of recombinant bacteria can be somewhat affected by the longer gene length of pgsA (1,143 bp); therefore, a truncated gene, pgsA, was generated based on the characteristics of pgsA by computational analysis. Using murine IL-10 as an exogenous gene, recombinant Lactobacillus plantarum was constructed and the capacity of the surface-displayed protein and functional differences between exogenous proteins expressed by these strains were evaluated. Surface expression of IL-10 on both recombinant bacteria with anchorins and the higher expression levels in L. plantarum-pgsA'-IL-10 were confirmed by western blot assay. Most importantly, up-regulation of IL-1β, IL-6, TNF-α, IFN-γ, and the nuclear transcription factor NF-κB p65 in RAW264.7 cells after stimulation with Poly(I:C) or LPS was exacerbated after co-culture with L. plantarum-pgsA. By contrast, IL-10 expressed by these recombinant strains could reduce these factors, and the expression of these factors was associated with recombinant strains that expressed anchorin (especially in L. plantarum-pgsA'-IL-10) and was significantly lower compared with the anchorin-free strains. These findings indicated that exogenous proteins could be successfully displayed on the surface of L. plantarum by pgsA or pgsA', and the expression of recombinant bacteria with pgsA' was superior compared with bacteria with pgsA.

  2. Levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in familial Mediterranean fever (FMF) patients and their first degree relatives.

    Science.gov (United States)

    Oktem, S; Yavuzsen, T U; Sengül, B; Akhunlar, H; Akar, S; Tunca, M

    2004-01-01

    Familial Mediterranean Fever (FMF) is a hereditary disease characterized by recurrent inflammatory attacks. A subclinical inflammation may persist in periods between the attacks and heterozygotes may have higher than normal levels of acute phase proteins. We investigated the levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in FMF patients and their obligatory carrier relatives. Serum levels of IL-6 and sIL-6R were measured during acute attacks (n = 18) and in attack-free FMF patients (n = 26), obligatory carriers of FMF (n = 17) and normal controls (n = 11). The median levels of IL-6 were significantly higher (45.71 pg/ mL, p = 0.001) during acute attacks of FMF only, and were normal (0.01 pg/ mL) in the other groups studied. There was no statistically significant difference in the median sIL-6R values between any of the groups (p = 0.22). IL-6 was extremely elevated during FMF attacks but could not detect hypothetical "subclinical" inflammation during attack-free intervals or in the heterozygote relatives of patients. Serum levels of sIL-6R were comparable in all four groups.

  3. Serum Levels of IL-6 Type Cytokines and Soluble IL-6 Receptors in Active B-Cell Chronic Lymphocytic Leukemia and in Cladribine Induced Remission

    Directory of Open Access Journals (Sweden)

    T. Robak

    1999-01-01

    Full Text Available We have investigated the serum concentrations of interleukin-6 (IL-6 and two IL-6 family cytokines-oncostatin M (OSM and leukemia inhibitory factor (LIF-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R and glycoprotein 130 (sgp130. The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA, as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL-6 serum level with the concentration of OSM and IL-6 soluble receptors. IL-6 was measurable in 62/63 (98.4%, OSM in 20/25 (80% of untreated and 14/38 (37.8% of the treated patients. sIL-6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P>0.05. However, in the patients treated with 2-CdA the IL-6 level was significantly lower (P0.05. We have found significant positive correlation between the levels of sIL6R and the lymphocytes count in CLL patients (Ρ=0.423; P<0.001. In addition, sIL-6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, are useful indicators of CLL activity.

  4. In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice

    DEFF Research Database (Denmark)

    Rasmussen, Per; Vedel, J-C; Olesen, J

    2011-01-01

    . Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels. Methods: Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined....... The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8). Results: At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1 h...

  5. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Harder-Lauridsen, Nina Majlund; Krogh-Madsen, R; Holst, J J;

    2014-01-01

    Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would...... increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h...... in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 (P

  6. The role of intratumoral and systemic IL-6 in breast cancer

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Højfeldt, Grith Westergaard; Hojman, Pernille

    2013-01-01

    circulating IL-6 and risk of breast cancer, prognosis for patients with prevalent disease, adverse effects and interventions to control systemic IL-6 levels in patients are discussed. In summary, direct application of IL-6 on breast cancer cells inhibits proliferation in estrogen receptor positive cells......, while high circulating IL-6 levels are correlated with a poor prognosis in breast cancer patients. This discrepancy reflects distinct roles of IL-6, with elevated systemic levels being a biomarker for tumor burden, physical inactivity, and impaired metabolism, while local intratumoral IL-6 signaling......Chronic low-grade inflammation plays an important role in the pathogenesis of several cancer forms including breast cancer. The pleiotropic cytokine IL-6 is a key player in systemic inflammation, regulating both the inflammatory response and tissue metabolism during acute stimulations. Here, we...

  7. Beneficial potential of intravenously administered IL-6 in improving outcome after murine experimental stroke

    DEFF Research Database (Denmark)

    Grønhøj, Mads Byskov; Clausen, Bettina Hjelm; Fenger, Christina

    2017-01-01

    IL-6 receptor (sIL-6R) alone or in combination, early after permanent middle cerebral artery occlusion (pMCAo) in mice. IL-6 did not affect the infarct volume in C57BL/6 mice, at neither 24 nor 72 h after pMCAo but reduced the infarct volume in IL-6 knockout mice at 24 h after pMCAo. Assessment...... pMCAo. Co-administration of IL-6 and sIL-6R increased the infarct volume, the number of infiltrating polymorphonuclear leukocytes and impaired the rotarod endurance ofC57BL/6mice 24 h after pMCAo. IL-6 administration to naïve C57BL/6 mice lead after 45 minutes to increased plasma-levels of CXCL1...

  8. Arcobacter butzleri Induce Colonic, Extra-Intestinal and Systemic Inflammatory Responses in Gnotobiotic IL-10 Deficient Mice in a Strain-Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Greta Gölz

    Full Text Available The immunopathological impact of human Arcobacter (A. infections is under current debate. Episodes of gastroenteritis with abdominal pain and acute or prolonged watery diarrhea were reported for A. butzleri infected patients. Whereas adhesive, invasive and cytotoxic capacities have been described for A. butzleri in vitro, only limited information is available about the immunopathogenic potential and mechanisms of infection in vivo.Gnotobiotic IL-10-/- mice were generated by broad-spectrum antibiotic treatment and perorally infected with the A. butzleri strains CCUG 30485 and C1 shown to be invasive in cell culture assays. Bacterial colonization capacities, clinical conditions, intestinal, extra-intestinal and systemic immune responses were monitored at day six and 16 postinfection (p.i.. Despite stable intestinal A. butzleri colonization at high loads, gnotobiotic IL-10-/- mice were virtually unaffected and did not display any overt symptoms at either time point. Notably, A. butzleri infection induced apoptosis of colonic epithelial cells which was paralleled by increased abundance of proliferating cells. Furthermore A. butzleri infection caused a significant increase of distinct immune cell populations such as T and B cells, regulatory T cells, macrophages and monocytes in the colon which was accompanied by elevated colonic TNF, IFN-γ, nitric oxide (NO, IL-6, IL-12p70 and MCP-1 concentrations. Strikingly, A. butzleri induced extra-intestinal and systemic immune responses as indicated by higher NO concentrations in kidney and increased TNF, IFN-γ, IL-12p70 and IL-6 levels in serum samples of infected as compared to naive mice. Overall, inflammatory responses could be observed earlier in the course of infection by the CCUG 30485 as compared to the C1 strain.Peroral A. butzleri infection induced not only intestinal but also extra-intestinal and systemic immune responses in gnotobiotic IL-10-/- mice in a strain-dependent manner. These findings

  9. Effects of IL-6 on the development of zygote in mice after controlled ovarian hyperstimulation

    Directory of Open Access Journals (Sweden)

    Chun-hua WEI

    2016-04-01

    Full Text Available Objective  To study the effect of IL -6 on the development of zygotes of mice after controlled ovarian hyperstimulation. Methods  The present experiment included three parts: a Addition of IL-6: 80 female ICR mice were divided into 7 groups by random number table including 6 groups of superovulation (10 each and a group of natural ovulation cycle (n=20. According to addition of IL-6 in different concentration to culture media, the superovulated ICR mice were divided into superovulation control group (0pg/ml IL -6 group, 1pg/ml IL-6 group, 5pg/ml IL-6 group, 10pg/ml IL -6 group, 25pg/ml IL-6 group, and 50pg/ml IL-6 group, with ICR mice in natural ovulation cycle served as control. b Addition of IL-6 receptor antibody (RA: 90 female ICR mice were divided into 7 groups according to the random number table, including 5 groups of superovulation (10 each on the basis of addition of different concentrations IL-6 and IL-6 RA to culture media (0pg/ml IL-6+RA groups, 1pg/ml IL-6+RA group, 5pg/ml IL-6+RA group, 10pg/ml IL-6+RA group, 25pg/ml IL-6+RA group, and 2 groups of normal natural cycle (20 each, including control group and the control group+IL -6 RA (100pg/ml group. Mice in normal control group conceived naturally while those in superovulation group conceived after superovulation. The zygotes were collected and cultured in vitro for 1 day till the formation of 2-cell embryos, then the rate of 2-cell formation was observed under microscope. Experiments of each group were repeated three times. c Immunofluorescence identification: 10 female ICR mice were divided into control group and superovulation group (5 each by random number table method. The expressions of IL -6 in zygotes were determined with confocal immunofluorescence method. Results  IL-6 addition experiment: the rate of 2-cell formation was significantly lower (P<0.05 in superovulated control group, 1pg/ml IL -6, 25pg/ml IL -6 and 50pg/ml IL-6 groups than in control group (P=0.023, P=0

  10. Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy

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    Sui-Ling Liao

    2016-01-01

    Full Text Available Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OHD level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OHD levels (r=0.67, p<0.001. Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 (p=0.004 and TLR7-8 stimulation (p=0.006. However, none of the TLR-triggered cytokine productions were associated with cord 25(OHD concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

  11. IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Öhman, H.; Tiitinen, A; Halttunen, M.

    2006-01-01

    Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic...... background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different...... IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-gamma responses were found in subjects with IL-10 -1082 GG genotype when compared to those with -1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells...

  12. Wilms' tumor protein Wt1 regulates the Interleukin-10 (IL-10) gene.

    Science.gov (United States)

    Sciesielski, Lina K; Kirschner, Karin M; Scholz, Holger; Persson, Anja Bondke

    2010-11-19

    We identified the Wilms' tumor protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.

  13. Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men.

    Science.gov (United States)

    Eklund, Carita; Nenonen, Arja; Kukkonen-Harjula, Katriina; Borg, Patrik; Fogelholm, Mikael; Laine, Seppo; Huhtala, Heini; Lehtimäki, Terho; Hurme, Mikko

    2006-06-01

    Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3,954(C/T) and CRP +1,059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72 obese men who had participated in a weight reduction program. Their C-reactive protein concentrations, interleukin-6 levels and fat mass were determined at two time points: at baseline and after weight reduction (after 2 months). After weight reduction, the mean weight loss was 14.3 kg. Median C-reactive protein concentrations decreased, after weight reduction, from 1.72 to 1.22 mg/l (p polymorphisms studied were not associated with CRP concentrations. Our results show that, at baseline, there is no difference in C-reactive protein concentrations among the different IL6-174(G/C) genotypes, but after weight loss the CC genotype is associated with highest C-reactive protein concentrations, resulting from the fact that C-reactive protein seems not to decrease with weight loss in this genotype.

  14. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Science.gov (United States)

    Wang, Zhi-Yong; Zhang, Jun-Ai; Wu, Xian-Jin; Liang, Yan-Fang; Lu, Yuan-Bin; Gao, Yu-Chi; Dai, You-Chao; Yu, Shi-Yan; Jia, Yan; Fu, Xiao-Xia; Rao, Xiaoquan; Xu, Jun-Fa

    2016-01-01

    Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. PMID:27006530

  15. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  16. Lack of IL-6 increases blood–brain barrier permeability in fungal meningitis

    Indian Academy of Sciences (India)

    Xiang Li; Guiyang Liu; Jianli Ma; Liang Zhou; Qingzhe Zhang; Lei Gao

    2015-03-01

    The pathogenesis of increased blood–brain barrier permeability during Cryptococcus meningitis is still largely unknown. Interleukin (IL-6) is a multifunctional cytokine, and numerous studies have shown that IL‐6 influences the integrity of the blood–brain barrier. In this study we investigated the role of IL-6 in Cryptococcus meningitis. First, wild-type or IL-6−/− mice were injected with Cryptococcus neoformans (C. neoformans) and the survival time in both groups was recorded. Second, the number of fungi was measured in the brains of IL-6−/− wild-type mice. Finally, the blood–brain barrier permeability index was detected in infected IL-6−/− mice treated with recombinant human IL-6. The blood–brain barrier permeability index was measured in infected wild-type mice treated with anti-IL-6 antibodies as well. The survival of IL-6−/− mice injected with C. neoformans was significantly lower than that of identically challenged wild-type mice. The infected IL-6−/− mice had significantly larger brain fungal burdens than wild-type mice. Furthermore, increased blood–brain barrier index was found in infected IL-6−/− mice when compared with that in infected control mice. Similar results were obtained when mice challenged with C. neoformans were treated systemically with neutralizing anti-IL-6 antibodies, resulting in an elevation of vascular permeability. Our data revealed that IL-6 reduced the blood–brain barrier permeability during Cryptococcus meningitis, and it might provide an explanation for the significantly lower survival of infected IL-6−/− mice.

  17. IL-6 Mediates the Intestinal Microvascular Thrombosis Associated with Experimental Colitis.

    Science.gov (United States)

    Hozumi, Hideaki; Russell, Janice; Vital, Shantel; Granger, D Neil

    2016-03-01

    Inflammatory bowel diseases are associated with increased risk for thrombus formation both within the inflamed bowel and at distant sites. Although the increased propensity for distant organ thrombus development has been recapitulated in animal models of colitis and linked to interleukin-6 (IL-6), it remains unclear whether experimental colitis results in accelerated thrombus development within the inflamed bowel and whether IL-6 contributes to a local thrombogenic response. These issues related to thrombus formation within the inflamed bowel were addressed in mice with dextran sodium sulfate-induced colitis. Wild-type (WT) mice, IL-6 deficient (IL-6(-/-)) mice, and bone marrow chimeras (WT→WT and IL-6(-/-)→WT) were used. The effects of treatment with either an IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody were also evaluated. Disease activity index and colonic weight-to-length ratio (W/L) were used to monitor the development of colitis. Intravital videomicroscopy was used to study thrombus development (induced with the light/dye method) in mucosal vessels of the ascending colon. Thrombus development was significantly enhanced in WT colitic mice. Neither genetic deficiency nor immunoblockade of IL-6 significantly altered the disease activity index and W/L responses to dextran sodium sulfate treatment. However, colitis-induced thrombogenesis was attenuated in IL-6(-/-) mice and in WT mice treated with either the IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody. IL-6(-/-)→WT, but not WT→WT chimeras, exhibited a blunted thrombosis response to dextran sodium sulfate. These results indicate that experimental colitis is associated with accelerated thrombus development within the inflamed colon and that IL-6, derived from bone marrow-derived blood cells, is largely responsible for this response.

  18. IL-10 inhibits while calcitriol reestablishes placental antimicrobial peptides gene expression.

    Science.gov (United States)

    Olmos-Ortiz, Andrea; Noyola-Martínez, Nancy; Barrera, David; Zaga-Clavellina, Verónica; Avila, Euclides; Halhali, Ali; Biruete, Benjamín; Larrea, Fernando; Díaz, Lorenza

    2015-04-01

    IL-10 and calcitriol help to achieve a successful pregnancy by suppressing active maternal immunity; however, these factors exert opposite effects upon microbial infections. In the skin and immune cells, IL-10 downregulates β-defensins while calcitriol induces cathelicidin gene expression in various tissues including placenta. Though, the regulation of human placental β-defensins by IL-10 and calcitriol has not been studied. Therefore, we explored the regulation of these antimicrobial peptides expression in cultured placental cells by calcitriol and IL-10 alone and combined. Real time PCR showed that calcitriol stimulated, while IL-10 inhibited, β-defensins and cathelicidin gene expression (Pantimicrobial peptides gene expression above control values, overriding IL-10 inhibitory effects. Calcitriol downregulated endogenous IL-10 secretion. Interestingly, calcitriol and TNF-α cooperatively enhanced β-defensins, while TNF-α reduced basal and calcitriol-stimulated cathelicidin gene expression. In summary, calcitriol and IL-10 exerted opposite effects on antimicrobial peptides expression in the human placenta, suggesting that unbalanced production of IL-10 and calcitriol could be deleterious to innate immune responses during gestation. Our results suggest that calcitriol enhancement of placental defenses involves two mechanisms: (1) downregulation of IL-10 secretion and (2) direct upregulation of β-defensins and cathelicidin gene expression. Considering that IL-10 and calcitriol differentially regulate the innate immune response in the placenta, in the case of an infection, calcitriol might restrict IL-10 permissive actions towards microbial invasion while restrains inflammation, allowing for pregnancy to continue in quiescence. These results strongly advice maternal vitamin D sufficiency during pregnancy.

  19. The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    E. Fisic

    2013-01-01

    Full Text Available Background and Aim. Early assessment of severity in acute pancreatitis (AP is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of interleukins (IL 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr, pancreatic elastase (E1, and C-reactive protein (CRP as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (. CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day ( and , resp.. Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.

  20. The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis.

    Science.gov (United States)

    Fisic, E; Poropat, G; Bilic-Zulle, L; Licul, V; Milic, S; Stimac, D

    2013-01-01

    Background and Aim. Early assessment of severity in acute pancreatitis (AP) is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of interleukins (IL) 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr), pancreatic elastase (E1), and C-reactive protein (CRP) as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (P = 0.001). CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day (P = 0.002 and P = 0.001, resp.). Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.

  1. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    Science.gov (United States)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-02-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

  2. Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yi Luo

    2012-01-01

    Full Text Available Problem statement: Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis Bacillus Calmette-Guerin (BCG is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not desirable with respect to its efficacy and side effects. Interleukin (IL-10, a T helper type (Th 2 cytokine, plays an important regulatory role in bladder cancer immunosurveillance and BCG immunotherapy. Therefore, blocking IL-10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. Approach: Treatment with intravesical BCG in combination with systemic IL-10 monoclonal antibody (mAb specific for IL-10 neutralization or IL-10 receptor (IL-10R blockage has been evaluated in preclinical bladder cancer models. Results: Addition of anti-IL-10 neutralizing mAb or anti-IL-10R1 mAb enhances BCG induction of Th1 immune responses and anti-bladder cancer immunity. Conclusion/Recommendations: BCG immunotherapy of bladder cancer can be enhanced by addition of IL-10 blocking mAb. Future studies should aim to explore the mechanisms underlying the induction of enhanced antitumor immunity by BCG combination therapy and develop therapeutic regimens for clinical evaluation of the safety and efficacy of BCG combination therapy.

  3. Detection of IL-6 in human milk and its involvement in IgA production.

    Science.gov (United States)

    Saito, S; Maruyama, M; Kato, Y; Moriyama, I; Ichijo, M

    1991-09-01

    A large amount of interleukin-6 (IL-6) was found to be contained in human whey. The concentration of IL-6 in colostrum was significantly higher than that in serum or in milk taken 1 month after parturition. Colostrum contained many more mononuclear cells than late milk. In terms of the proportion of monocytes, T cells and B cells, however, there is no difference between colostrum and late milk. There is a significantly positive correlation between the concentration of IL-6 and the number of mononuclear cells in milk. This demonstrates that IL-6 in whey is derived in part from mononuclear cells. Stimulation of human milk mononuclear cells by Staphylococcus aureus Cowan I in the presence of anti-IL-6 antibody markedly decreased the production of IgA. This suggests that IL-6 contained in milk is closely associated with the local production of IgA in the breast.

  4. Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling

    DEFF Research Database (Denmark)

    Westberg, Johan A; Serlachius, Martina; Lankila, Petri

    2007-01-01

    . Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We...... mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc......-1 in brains of wild-type but not of IL-6-deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells...

  5. Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup; Knudsen, Jakob Grunnet; Brandt, Nina

    2014-01-01

    Skeletal muscle regulates substrate choice according to demand and availability and pyruvate dehydrogenase (PDH) is central in this regulation. Circulating interleukin (IL)-6 increases during exercise and IL-6 has been suggested to increase whole body fat oxidation. Furthermore, IL-6 has been...... not affect plasma glucose or muscle glycogen, but increased AMPK and ACC phosphorylation and tended to decrease p38 protein content in skeletal muscle in fasted mice. In addition IL-6 injection reduced PDHa activity in fed mice and increased PDHa activity in fasted mice without significant changes in PDH-E1α...... reported to increase AMP-activated protein kinase (AMPK) phosphorylation and AMPK suggested to regulate PDHa activity. Together, this suggests that IL-6 may be involved in regulating PDH. The aim of this study was to investigate the effect of a single injection of IL-6 on PDH regulation in skeletal muscle...

  6. Notch ligand delta-like 4-pretreated dendritic cells alleviate allergic airway responses by enhancing IL-10 production.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Huang

    Full Text Available The Notch pathway plays a role in the processes of cell proliferation, differentiation, and apoptosis, which affect the development and function of various organs. Dendritic cells (DCs, as professional antigen-presenting cells (APCs, induce T cell activation and promote T cell differentiation by antigen stimulation. Research has shown that Notch ligand delta-like 4 (Dll4 in APCs is associated with stimulation of a Th1-type response. However, the regulatory roles of Dll4 in the activation and function of DCs have yet to be clearly elucidated. In this study, we demonstrated that activation of Dll4-pretreated bone marrow-derived DCs by performing ovalbumin (OVA stimulation expressed a high level of interleukin (IL-10 without diminishing IL-12 production. By contrast, the proinflammatory cytokines, IL-1β, IL-6, and tumor necrosis factor (TNF-α, decreased in Dll4-pretreated DCs by performing either lipopolysaccharide (LPS or OVA stimulation. Compared to fully mature DCs, lower levels of MHC class II CD40 and higher levels of CD80 and CD86 molecules were expressed in these semi-mature like DCs. Dll4 Notch signaling also enhanced Notch ligand mRNA expression of Dll1, Dll4, and Jagged1 in DCs. Dll4-modified DCs exhibited a reduced capacity to stimulate the proliferation of OVA-specific CD4(+ T cells, but actively promoted large amounts of IL-10 production in these activated T cells. Furthermore, immunomodulatory effects of Dll4-modified DCs were examined in an established asthmatic animal model. After adoptive transfer of OVA-pulsed plus Dll4-pretreated DCs in OVA-immunized mice, OVA challenge induced lower OVA-specific immunoglobulin E (IgE and higher IgG2a antibody production, lower eotaxin, keratinocyte-derived chemokine (KC, IL-5, and IL-13 release in bronchial alveolar lavage fluid, attenuated airway hyper-responsiveness, and promoted higher IL-10 and interferon (IFN-γ production in the spleen. In summary, our findings elucidate the new role of

  7. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

  8. Sex differences in the relationship of IL-6 signaling to cancer cachexia progression.

    Science.gov (United States)

    Hetzler, Kimbell L; Hardee, Justin P; Puppa, Melissa J; Narsale, Aditi A; Sato, Shuichi; Davis, J Mark; Carson, James A

    2015-05-01

    A devastating aspect of cancer cachexia is severe loss of muscle and fat mass. Though cachexia occurs in both sexes, it is not well-defined in the female. The Apc(Min/+) mouse is genetically predisposed to develop intestinal tumors; circulating IL-6 is a critical regulator of cancer cachexia in the male Apc(Min/+) mouse. The purpose of this study was to examine the relationship between IL-6 signaling and cachexia progression in the female Apc(Min/+) mouse. Male and female Apc(Min/+) mice were examined during the initiation and progression of cachexia. Another group of females had IL-6 overexpressed between 12 and 14 weeks or 15-18 weeks of age to determine whether IL-6 could induce cachexia. Cachectic female Apc(Min/+) mice lost body weight, muscle mass, and fat mass; increased muscle IL-6 mRNA expression was associated with these changes, but circulating IL-6 levels were not. Circulating IL-6 levels did not correlate with downstream signaling in muscle in the female. Muscle IL-6r mRNA expression and SOCS3 mRNA expression as well as muscle IL-6r protein and STAT3 phosphorylation increased with severe cachexia in both sexes. Muscle SOCS3 protein increased in cachectic females but decreased in cachectic males. IL-6 overexpression did not affect cachexia progression in female Apc(Min/+) mice. Our results indicate that female Apc(Min/+) mice undergo cachexia progression that is at least initially IL-6-independent. Future studies in the female will need to determine mechanisms underlying regulation of IL-6 response and cachexia induction.

  9. The Inhibitory Effect of Quercetin on IL-6 Production by LPS-Stimulated Neutrophils

    Institute of Scientific and Technical Information of China (English)

    Jiajia Liu; Xin Li; Yang Yue; Juan Li; Tao He; Yanzheng He

    2005-01-01

    Quercetin is a herbal flavonoid derived from various foods of plant origin and plays a role in anti-inflammation. Although a number of researches in the field have been done, the mechanism of anti-inflammatory effect of quercetin should be further clarified. In the present study, we investigated the effects of quercetin on IL-6 production by LPS-stimulated neutrophils in human. Neutrophils were were pre-treated with quercetin at the final concentrations of ranging from 0-80 μM for 30 min, or not treated, and then incubated in the presence or absence of lipopolysaccharide (LPS) at a final concentration of 100 ng/ml for indicated time. The secretion level of IL-6 in the culture supernatants was assayed by ELISA, the intracellular level of IL-6 was detected by flow cytometry and the expression of IL-6 mRNA was analyzed by RT-PCR. The experiment results showed that neutrophils cultured with medium or quercetin alone did not express IL-6, but LPS (100 ng/ml) induced IL-6 expression of neutrophils. However, after pre-treatment of neutrophils with quercetin (40 μM) for 30 min, the inducible effects of LPS on the increase of IL-6 secretion, intracellular IL-6 level and IL-6 mRNA expression by neutrophils were abrogated. IL-6 is one of the important pro-inflammatory factors, especially in early phage of inflammation. Thus, our data suggested that quercetin might exert its anti-inflammatory effect through negatively modulating pro-inflammatory factors, such as IL-6. The inhibitory effects of quercetin on IL-6 production by neutrophils may provide a theoretical basis on future therapy of inflammation.

  10. Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types.

    Science.gov (United States)

    Noss, Erika H; Nguyen, Hung N; Chang, Sook Kyung; Watts, Gerald F M; Brenner, Michael B

    2015-12-01

    Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14(+) monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6-producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types.

  11. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    OpenAIRE

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained vir...

  12. A three base pair gene variation within the distal 5'-flanking region of the interleukin-10 (IL-10) gene is related to the in vitro IL-10 production capacity of lipopolysaccharide-stimulated peripheral blood mononuclear cells.

    NARCIS (Netherlands)

    Rieth, H.; Mormann, M.; Luty, J.F.; Assohou-Luty, C.A.; Roupelieva, M.; Kremsner, P.G.; Kube, D.

    2004-01-01

    Interleukin-10 (IL-10) is an important multifunctional immunmodulator. There is evidence that IL-10 secretion is associated with certain genetic elements of the proximal IL-10 gene 5'-flanking region. The allelic and genotypic comparison of IL-10 expression by lipopolysaccharide (LPS)- stimulated le

  13. Anti-IL-6 receptor antibody does not ameliorate radiation pneumonia in mice

    Science.gov (United States)

    OGATA, TOSHIYUKI; YAMAZAKI, HIDEYA; TESHIMA, TERUKI; TSUCHIYA, TAKAHIRO; NISHIMOTO, NORIHIRO; MATSUURA, NARIAKI

    2012-01-01

    We previously showed that early administration of monoclonal anti-interleukin-6 receptor antibody (IL-6RA) does not prevent radiation-induced lung injury in mice. The purpose of this study was to investigate whether a higher dose and longer course of IL-6RA treatment was effective in ameliorating radiation pneumonia. C57Bl/6J mice received thoracic irradiation of 12 Gy, and were intraperitoneally injected with the IL-6RA, namely MR16-1, or with control rat IgG 4 times, once immediately following exposure and then weekly from 1 to 3 weeks after irradiation. Enzyme-linked immunosorbent assays were used to analyze the plasma levels of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin (H&E) and by measuring wet lung weight. We observed marked upregulation of IL-6 in IL-6RA-treated mice compared to the IgG-treated control group, whereas IL-6RA did not increase the production of SAA in the group receiving irradiation. However, radiation pneumonia, as evaluated by H&E staining and lung weight showed no differences between the IL-6RA-treated mice and the controls. Long-term treatment with high-dose IL-6RA does not ameliorate radiation pneumonia. PMID:22984368

  14. Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Lago, Natalia

    2003-01-01

    . This study demonstrated that transgenic IL-6 production significantly increased wound healing following the cryolesion. Thus, at 20 days postlesion (dpl) the GFAP-IL6 mice showed almost complete wound healing compared to litter mate nontransgenic controls. It seems likely that a reduced inflammatory response...... in the long term could be responsible for this IL-6-related effect. Thus, while in the acute phase following cryolesion (1-6 dpl) the recruitment of macrophages and T lymphocytes was higher in GFAP-IL6 mice, at 10-20 dpl it was significantly reduced compared to controls. Reactive astrogliosis was also...

  15. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P;

    1995-01-01

    injury. In the current study, we sought to determine whether endogenous IL-10 is playing a regulatory role in the lung inflammatory response. On the basis of lung mRNA and ELISA measurements, IL-10 induction was found during development of inflammation in the IgG immune complex model of lung injury...

  16. Role of Blimp-1 in programing Th effector cells into IL-10 producers.

    Science.gov (United States)

    Neumann, Christian; Heinrich, Frederik; Neumann, Katrin; Junghans, Victoria; Mashreghi, Mir-Farzin; Ahlers, Jonas; Janke, Marko; Rudolph, Christine; Mockel-Tenbrinck, Nadine; Kühl, Anja A; Heimesaat, Markus M; Esser, Charlotte; Im, Sin-Hyeog; Radbruch, Andreas; Rutz, Sascha; Scheffold, Alexander

    2014-08-25

    Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T cells is an essential mechanism of self-limitation during infection. However, the transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1 cells is insufficiently understood. We report a crucial role for the transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner, in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive inflammation during Toxoplasma gondii infection with increased mortality. IL-10 production from Th1 cells was strictly dependent on Blimp-1 but was further enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL-10 induced by multiple factors, such as the Notch pathway. We found Blimp-1 expression, which was also broadly induced by IL-27 in effector T cells, to be antagonized by transforming growth factor (TGF) β. While effectively blocking IL-10 production from Th1 cells, TGF-β shifted IL-10 regulation from a Blimp-1-dependent to a Blimp-1-independent pathway in IL-27-induced Tr1 (T regulatory 1) cells. Our findings further illustrate how IL-10 regulation in Th cells relies on several transcriptional programs that integrate various signals from the environment to fine-tune expression of this critical immunosuppressive cytokine. © 2014 Neumann et al.

  17. Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes

    NARCIS (Netherlands)

    Stoger, J. Lauran; Boshuizen, Marieke C. S.; Brufau, Gemma; Gijbels, Marion J. J.; Wolfe, Ine M. J.; van der Velden, Saskia; Pottgens, Chantal C. H.; Vergouwe, Monique N.; Wijnands, Erwin; Beckers, Linda; Goossens, Pieter; Kerksiek, Anja; Havinga, Rick; Muller, Werner; Luetjohann, Dieter; Groen, Albert K.; de Winther, Menno P. J.

    2016-01-01

    Inflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be d

  18. Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

    DEFF Research Database (Denmark)

    Kaneko, Tetsushi; Itoh, Masahiro; Nakamura, Yoichi;

    2003-01-01

    We studied the effects of exogenously administered recombinant murine interleukin (IL)-10 on the development of experimental autoimmune orchitis (EAO) in C3H/He mice. IL-10 significantly augments histological signs of EAO when administered for 6 consecutive days from days 15 to 20 after primary...

  19. First identification of regulatory B cell subsets expressing IL-10 in teleost fish

    Science.gov (United States)

    IL-10 is an immunoregulatory cytokine with a potent anti-inflammatory activity, thus inhibiting the production of proinflammatory cytokines as well as processes of antigen presentation. IL-10 is produced by variety of cells, including antigen presentation cells (i.e., monocytes, macrophages and den...

  20. IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

    Science.gov (United States)

    Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

    2009-06-30

    Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

  1. Molecular cloning and expression of the IL-10 gene from guinea pigs.

    Science.gov (United States)

    Dirisala, Vijaya R; Jeevan, Amminikutty; Bix, Gregory; Yoshimura, Teizo; McMurray, David N

    2012-04-25

    The Guinea pig (Cavia porcellus) is one of the most relevant small animals for modeling human tuberculosis (TB) in terms of susceptibility to low dose aerosol infection, the organization of granulomas, extrapulmonary dissemination and vaccine-induced protection. It is also considered to be a gold standard for a number of other infectious and non-infectious diseases; however, this animal model has a major disadvantage due to the lack of readily available immunological reagents. In the present study, we successfully cloned a cDNA for the critical Th2 cytokine, interleukin-10 (IL-10), from inbred Strain 2 guinea pigs using the DNA sequence information provided by the genome project. The complete open reading frame (ORF) consists of 537 base pairs which encodes a protein of 179 amino acids. This cDNA sequence exhibited 87% homology with human IL-10. Surprisingly, it showed only 84% homology with the previously published IL-10 sequence from the C4-deficient (C4D) guinea pig, leading us to clone IL-10 cDNA from the Hartley strain of guinea pig. The IL-10 gene from the Hartley strain showed 100% homology with the IL-10 sequence of Strain 2 guinea pigs. In order to validate the only published IL-10 sequence existing in Genbank reported from C4D guinea pigs, genomic DNA was isolated from tissues of C4D guinea pigs. Amplification with various sets of primers showed that the IL-10 sequence reported from C4D guinea pigs contained numerous errors. Hence the IL-10 sequence that is being reported by us replaces the earlier sequence making our IL-10 sequence to be the first one accurate from guinea pig. Recombinant guinea pig IL-10 proteins were subsequently expressed in both prokaryotic and eukaryotic cells, purified and were confirmed by N-terminal sequencing. Polyclonal anti-IL-10 antibodies were generated in rabbits using the recombinant IL-10 protein expressed in this study. Taken together, our results indicate that the DNA sequence information provided by the genome project

  2. Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior.

    Science.gov (United States)

    Erta, Maria; Giralt, Mercedes; Esposito, Flavia Lorena; Fernandez-Gayol, Olaya; Hidalgo, Juan

    2015-07-01

    Interleukin-6 (IL-6) is a major cytokine in the central nervous system, secreted by different brain cells and with roles in a number of physiological functions. We herewith confirm and expand the importance of astrocytic production of and response to IL-6 by using transgenic mice deficient in astrocytic IL-6 (Ast-IL-6 KO) or in its receptor (Ast-IL-6R KO) in full C57Bl/6 genetic background. A major prosurvival effect of astrocytic IL-6 at early ages was clearly demonstrated. Robust effects were also evident in the control of activity and anxiety in the hole-board and elevated plus-maze, and in spatial learning in the Morris water-maze. The results also suggest an inhibitory role of IL-6 in the mechanism controlling the consolidation of hippocampus-dependent spatial learning. Less robust effects of astrocytic IL-6 system were also observed in despair behavior in the tail suspension test, and social behavior in the dominance and resident-intruder tests. The behavioral phenotype was highly dependent on age and/or sex in some cases. The phenotype of Ast-IL-6R KO mice mimicked only partially that of Ast-IL-6KO mice, which indicates both a role of astrocytes in behavior and the participation of other cells besides astrocytes. No evidences of altered function of the hypothalamic-pituitary-adrenal axis were observed. These results demonstrate that astrocytic IL-6 (acting at least partially in astrocytes) regulates normal behavior in mice.

  3. Influence of Atg5 mutation in SLE depends on functional IL-10 genotype.

    Directory of Open Access Journals (Sweden)

    Patricia López

    Full Text Available Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Despite the identification of autophagy-related protein (Atg-5 as one of the susceptibility loci in systemic Lupus erythematosus (SLE, the consequences of the carriage of these mutations for patients remain unclear. The present work analyzed the association of Atg5 rs573775 single nucleotide polymorphism (SNP with SLE susceptibility, IFNα, TNFα and IL-10 serum levels, and clinical features, in 115 patients and 170 healthy individuals. Patients who where carriers of the rs573775 T* minor allele presented lower IFNα levels than those with the wild genotype, whereas the opposite result was detected for IL-10. Thus, since IL-10 production was regulated by rs1800896 polymorphisms, we evaluated the effect of this Atg5 mutation in genetically high and low IL-10 producers. Interestingly, we found that the rs573775 T* allele was a risk factor for SLE in carriers of the high IL-10 producer genotype, but not among genetically low producers. Moreover, IL-10 genotype influences SLE features in patients presenting the Atg5 mutated allele. Specifically, carriage of the rs573775 T* allele led to IL-10 upregulation, reduced IFNα and TNFα production and a low frequency of cytopenia in patients with the high IL-10 producer genotype, whereas patients with the same Atg5 allele that were low IL-10 producers presented reduced amounts of all these cytokines, had a lower prevalence of anti-dsDNA antibodies and the latest onset age. In conclusion, the Atg5 rs573775 T* allele seems to influence SLE susceptibility, cytokine production and disease features depending on other factors such as functional IL-10 genotype.

  4. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol.

    Science.gov (United States)

    Suryanarayanan, A; Carter, J M; Landin, J D; Morrow, A L; Werner, D F; Spigelman, I

    2016-08-01

    Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.

  5. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population

    Directory of Open Access Journals (Sweden)

    Ana Maria Sampaio

    2015-07-01

    Conclusion: IL-6 and IL-4 expression variants seem to have an important role in GC risk mechanisms. This study provides preliminary evidence that IL-4 and IL-6 polymorphisms, although not directly linked to the disease, may be useful tools in the study of this multifactorial disease.

  6. Pulmonary inflammation after ethanol exposure and burn injury is attenuated in the absence of IL-6.

    Science.gov (United States)

    Chen, Michael M; Bird, Melanie D; Zahs, Anita; Deburghgraeve, Cory; Posnik, Bartlomiej; Davis, Christopher S; Kovacs, Elizabeth J

    2013-05-01

    Alcohol consumption leads to an exaggerated inflammatory response after burn injury. Elevated levels of interleukin-6 (IL-6) in patients are associated with increased morbidity and mortality after injury, and high systemic and pulmonary levels of IL-6 have been observed after the combined insult of ethanol exposure and burn injury. To further investigate the role of IL-6 in the pulmonary inflammatory response, we examined leukocyte infiltration and cytokine and chemokine production in the lungs of wild-type and IL-6 knockout mice given vehicle or ethanol (1.11 g/kg) and subjected to a sham or 15% total body surface area burn injury. Levels of neutrophil infiltration and neutrophil chemoattractants were increased to a similar extent in wild-type and IL-6 knockout mice 24 h after burn injury. When ethanol exposure preceded the burn injury, however, a further increase of these inflammatory markers was seen only in the wild-type mice. Additionally, signal transducer and activator of transcription-3 (STAT3) phosphorylation did not increase in response to ethanol exposure in the IL-6 knockout mice, in contrast to their wild-type counterparts. Visual and imaging analysis of alveolar wall thickness supported these findings and similar results were obtained by blocking IL-6 with antibody. Taken together, our data suggest a causal relationship between IL-6 and the excessive pulmonary inflammation observed after the combined insult of ethanol and burn injury.

  7. Splenic Stromal Cells from Aged Mice Produce Higher Levels of IL-6 Compared to Young Mice

    Science.gov (United States)

    Park, Jihyun; Miyakawa, Takuya; Shiokawa, Aya; Nakajima-Adachi, Haruyo; Hachimura, Satoshi

    2014-01-01

    Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly. PMID:24729663

  8. Role of the IL-6 gene in the etiopathogenesis of idiopathic scoliosis.

    Science.gov (United States)

    Nikolova, Svetla; Dikova, Milka; Dikov, Dobrin; Djerov, Assen; Dzhebir, Gyulnas; Atanasov, Ventseslav; Savov, Alexey; Kremensky, Ivo

    2015-01-01

    Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6). The G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS) and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and the IL-6 promoter polymorphism at -174 position (rs1800795 G/C) in Bulgarian population. Molecular detection of the IL-6 genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson's chi-squared test. Our case-control study revealed a statistically significant association between the IL-6 (-174 G/C) functional polymorphism and susceptibility to IS. In addition, a significant association between the IL-6 (-174 G/C) polymorphism and curve severity was detected. IL-6 gene could be considered as susceptibility and modifying factor of idiopathic scoliosis. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

  9. Clinical significance of detection of serum interleukin(IL-6),tumr necrosis factor and urine IL-6 and IL-8 levels in patients with hepatocirrhosis%肝硬化患者血清IL-6、TNF和尿液IL-6、IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    周彦

    2001-01-01

    目的探讨细胞因子在肝硬化发病中的作用.方法采用双抗体夹心Elisa法对54例肝硬化患者和35例正常人血清白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)和尿液IL-6、IL-8进行检测.结果肝硬化患者血清中IL-6、TNF和尿液IL-6、IL-8含量较对照组明显升高(P<0.01),血IL-6、TNF含量GN与尿液量白蛋白呈高度正相关:尿液IL-6、IL-8呈显著正相关(r=0.5728,P<0.05).结论肝硬化患者病程中TNF、IL-6、IL-8均处于高活性状态,IL-6与体液免疫反应亢进所致的免疫病理损伤有关,IL-6、IL-8、TNF参与肾脏的免疫损伤、可作为判定患者预后和转归指标.

  10. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

    NARCIS (Netherlands)

    Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotyp

  11. Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

    Science.gov (United States)

    Sun, Xuan; Zhang, Jie; Wang, Zhiyong; Ji, Wei; Tian, Ran; Zhang, Fei; Niu, Ruifang

    2017-01-01

    Accumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors. However, whether Shp2 is involved in IL-6-signaling-promoted breast cancer EMT and progression, remains undefined. In this study, we showed that exogenous and endogenous IL-6 can enhance breast cancer invasion and migration, through the promotion of EMT. IL-6 also induces the activation of Erk1/2 and the phosphorylation of Shp2. Knockdown of Shp2 attenuated the IL-6-induced downregulation of E-cadherin, as well as IL-6-promoted cell migration and invasion. Moreover, by using Shp2 phosphatase mutants, phosphor-tyrosine mimicking, and deficiency mutants, we provided evidence that the phosphatase activity of Shp2 and its tyrosine phosphorylation, are necessary for the IL-6-induced downregulation of E-cadherin and the phosphorylation of Erk1/2. Our findings uncover an important function that links Shp2 to IL-6-promoted breast cancer progression. PMID:28208810

  12. Role of the IL-6 Gene in the Etiopathogenesis of Idiopathic Scoliosis

    Directory of Open Access Journals (Sweden)

    Svetla Nikolova

    2015-01-01

    Full Text Available Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6. The G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and the IL-6 promoter polymorphism at -174 position (rs1800795 G/C in Bulgarian population. Molecular detection of the IL-6 genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. Our case-control study revealed a statistically significant association between the IL-6 (-174 G/C functional polymorphism and susceptibility to IS. In addition, a significant association between the IL-6 (-174 G/C polymorphism and curve severity was detected. IL-6 gene could be considered as susceptibility and modifying factor of idiopathic scoliosis. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

  13. Changes of IL-6 and relevant cytokines in patients with hepatocellularcarcinoma and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    Cai Yah Zhao; Yue Lin Li; Su Xia Liu; Zhong Jun Feng

    2000-01-01

    AIM To study the changes of IL-6,IL-2, sIL-2R and TNF ir patients with hepatocellular carcinoma(HCC)and their clinical significance.METHODS IL-6, IL-2, sIL-2R and TNF were detected by avidin-biotin-system ELISA, double-sandwichELISA respectively in 60 patients with HCC and 36 patients with liver cirrhosis (LC) and 66 healthy persons.RESULTS The levels of IL-6, sIL-2R and TNF increased, but IL-2 level was lower in patients with HCCthan that in normal controls (NC) (t test, t=8.21, 4.71, 3.87, 2.13, P<0.01 or 0.05). IL-6 level in HCCwas 10 fold higher than NC, and also much higher than LC. IL-6 level was higher in later stage than that inearlier stage. There was a positive correlation between IL-6 and sIL-2R, TNF, while no positive correlationwas found between IL-2 and IL-6, sIL-2R in HCC.CONCLUSION The remarkably higher level of IL-6 is helpful for the early diagnosis of HCC.

  14. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis

    DEFF Research Database (Denmark)

    Gasim, S; Elhassan, A M; Khalil, E A

    1998-01-01

    Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We...... report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected...

  15. IL-6 Is Not Necessary for the Regulation of Adipose Tissue Mitochondrial Content

    Science.gov (United States)

    Wan, Zhongxiao; Perry, Christopher G. R.; Macdonald, Tara; Chan, Catherine B.; Holloway, Graham P.; Wright, David C.

    2012-01-01

    Background Adipose tissue mitochondria have been implicated as key mediators of systemic metabolism. We have shown that IL-6 activates AMPK, a mediator of mitochondrial biogenesis, in adipose tissue; however, IL-6−/− mice fed a high fat diet have been reported to develop insulin resistance. These findings suggest that IL-6 may control adipose tissue mitochondrial content in vivo, and that reductions in adipose tissue mitochondria may be causally linked to the development of insulin resistance in IL-6−/− mice fed a high fat diet. On the other hand, IL-6 has been implicated as a negative regulator of insulin action. Given these discrepancies the purpose of the present investigation was to further evaluate the relationship between IL-6, adipose tissue mitochondrial content and whole body insulin action. Methodology and Principal Findings In cultured epididymal mouse adipose tissue IL-6 (75 ng/ml) induced the expression of the transcriptional co-activators PGC-1α and PRC, reputed mediators of mitochondrial biogenesis. Similarly, IL-6 increased the expression of COXIV and CPT-1. These effects were absent in cultured subcutaneous adipose tissue and were associated with lower levels of GP130 and IL-6 receptor alpha protein content. Markers of mitochondrial content were intact in adipose tissue from chow fed IL-6−/− mice. When fed a high fat diet IL-6−/− mice were more glucose and insulin intolerant than controls fed the same diet; however this was not explained by decreases in adipose tissue mitochondrial content or respiration. Conclusions and Significance Our findings demonstrate depot-specific differences in the ability of IL-6 to induce PGC-1α and mitochondrial enzymes and demonstrate that IL-6 is not necessary for the maintenance of adipose tissue mitochondrial content in vivo. Moreover, reductions in adipose tissue mitochondria do not explain the greater insulin resistance in IL-6−/− mice fed a high fat diet. These results question the role of

  16. MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression.

    Science.gov (United States)

    Galbas, Tristan; Steimle, Viktor; Lapointe, Réjean; Ishido, Satoshi; Thibodeau, Jacques

    2012-07-01

    IL-10 is vastly studied for its anti-inflammatory properties on most immune cells. However, it has been reported that IL-10 activates B cells, up-regulates their MHC class II molecules and prevents apoptosis. As MARCH1 was shown to be responsible for the intracellular sequestration of MHC class II molecules in dendritic cells and monocytes in response to IL-10, we set out to clarify the role of this ubiquitin ligase in B cells. Here, we demonstrate in mice that splenic follicular B cells represent the major cell population that up-regulate MHC II molecules in the presence of IL-10. Activation of these cells through TLR4, CD40 or the IL-10 receptor caused the down-regulation of MARCH1 mRNA. Accordingly, B cells from MARCH1-deficient mice do not up-regulate I-A(b) in response to IL-10. In all, our results demonstrate that IL-10 can have opposite effects on MARCH1 regulation in different cell types.

  17. Micro RNA-19a suppresses IL-10 in peripheral B cells from patients with atherosclerosis.

    Science.gov (United States)

    Ren, Zhong-Qiao; Liu, Ning; Zhao, Kan

    2016-10-01

    The interleukin (IL)-10-production B cells play an important role in the pathogenesis of atherosclerosis (Asro) with unknown mechanism. Micro RNA (miR)-17-92 cluster has strong immune regulatory activities. This study tests a hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells of Asro patients. Patients with Asro were recruited into this study. Peripheral blood samples were collected from the patients. B cells were isolated from the blood samples and analyzed to elucidate the role of miR-17-92 in the regulation of IL-10 expression. Peripheral B cells from patients with Asro show lower levels of IL-10 than that from healthy subjects. The IL-10 expression in the B cells is negatively correlated with the expression of miR-19a in the B cells. The serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-4 in Asro patients were higher than healthy subjects. Exposure to TNF-α or IFN-γ or IL-4 suppressed IL-10 expression in B cells via increasing the expression of miR-19a in B cells, which could be abolished by Inhibition of miR-19a. TNF-α or IFN-γ or IL-4 suppresses IL-10 in B cells via up regulating miR-19a expression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. IL-10 polymorphism is associated with increased incidence of severe sepsis

    Institute of Scientific and Technical Information of China (English)

    SHU Qiang(舒 强); FANG Xiangming(方向明); CHEN Qixing(陈齐兴); Frank Stuber

    2003-01-01

    Objective To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis.Methods The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaⅠ, MaeⅢ and MnlⅠ, respectively.Results Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and heathy controls, nor between surviving and dead patients (P> 0.05). Conclusions The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In constrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.

  19. Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells.

    Science.gov (United States)

    Kvale, Espen O; Fløisand, Yngvar; Lund-Johansen, Fridtjof; Rollag, Halvor; Farkas, Lorant; Ghanekar, Smita; Brandtzaeg, Per; Jahnsen, Frode L; Olweus, Johanna

    2007-04-15

    Dendritic cells (DCs) are believed to regulate T cell-mediated immunity primarily by directing differentiation of naive T cells. Here, we show that a large fraction of CD4(+) memory cells produce IL-10 within the first hours after interaction with plasmacytoid DCs (PDCs). In contrast, CD11c(+) DCs induce IFN-gamma and little IL-10. IL-10-secreting T cells isolated after 36 hours of culture with PDCs suppressed antigen-induced T-cell proliferation by an IL-10-dependent mechanism, but were distinct from natural and type 1 regulatory T cells. They proliferated strongly and continued to secrete IL-10 during expansion with PDCs, and after restimulation with immature monocyte-derived DCs or CD11c(+) DCs. The IL-10-producing T cells acquired the ability to secrete high levels of IFN-gamma after isolation and subsequent coculture with PDCs or CD11c(+) DCs. Compared to CD11c(+) DCs, PDCs were superior in their ability to selectively expand T cells that produced cytokines on repeated antigenic challenge. The DC-dependent differences in cytokine profiles were observed with viral recall antigen or staphylococcal enterotoxin B and were independent of extracellular type I interferon or IL-10. Our results show that DCs can regulate memory responses and that PDCs rapidly induce regulatory cytokines in effector T cells that can suppress bystander activity.

  20. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    Science.gov (United States)

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

  1. The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection.

    Science.gov (United States)

    Hussain, Tariq; Shah, Syed Zahid Ali; Zhao, Deming; Sreevatsan, Srinand; Zhou, Xiangmei

    2016-12-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and is the causative agent of Johne's disease of domestic and wild ruminants. Johne's disease is characterized by chronic granulomatous enteritis leading to substantial economic losses to the livestock sector across the world. MAP persistently survives in phagocytic cells, most commonly in macrophages by disrupting its early antibacterial activity. MAP triggers several signaling pathways after attachment to pathogen recognition receptors (PRRs) of phagocytic cells. MAP adopts a survival strategy to escape the host defence mechanisms via the activation of mitogen-activated protein kinase (MAPK) pathway. The signaling mechanism initiated through toll like receptor 2 (TLR2) activates MAPK-p38 results in up-regulation of interleukin-10 (IL-10), and subsequent repression of inflammatory cytokines. The anti-inflammatory response of IL-10 is mediated through membrane-bound IL-10 receptors, leading to trans-phosphorylation and activation of Janus Kinase (JAK) family receptor-associated tyrosine kinases (TyKs), that promotes the activation of latent transcription factors, signal transducer and activators of transcription 3 (STAT3). IL-10 is an important inhibitory cytokine playing its role in blocking phagosome maturation and apoptosis. In the current review, we describe the importance of IL-10 in early phases of the MAP infection and regulatory mechanisms of the IL-10 dependent pathways in paratuberculosis. We also highlight the strategies to target IL-10, MAPK and STAT3 in other infections caused by intracellular pathogens.

  2. Breastfeeding and IL-10 levels in children affected by cow's milk protein allergy: A restrospective study.

    Science.gov (United States)

    Manti, Sara; Lougaris, Vassilios; Cuppari, Caterina; Tardino, Lucia; Dipasquale, Valeria; Arrigo, Teresa; Salpietro, Carmelo; Leonardi, Salvatore

    2017-02-01

    To assess the protective role of breast-feeding in infants with CMPA-related AEDS as well as IL-10 utility as marker of disease evolution. 64 breast-feeding children with CMPA-related AEDS (31 males and 33 females; mean age 5.56±2.41months; 21 mild AEDS; 25 moderate AEDS; 18 severe AEDS) and 60 artificial feeding babies (33 males and 27 females; mean age 6.01±2.08months; 26 mild AEDS; 19 moderate AEDS; 15 severe AEDS) were evaluated. In all patients serum IL-10 levels were detected. Significant Score Atopic Dermatitis (SCORAD) index point differences between breastfed and not breastfed children (p<0.001) have been detected. The serum IL-10 levels were lower in children with CMPA-related AEDS as compared to the healthy control group (p<0.001). Moreover, a significant inverse correlation between serum IL-10 levels and SCORAD in both enrolled groups has been also noted. In particular, IL-10 levels, in both groups, were significantly lower in children with severe symptoms. Conversely, serum IL-10 levels were significantly increased in children with mild-severe symptoms in both groups. Furthermore, breastfed children, with lower severe symptoms, had higher serum IL-10 levels. Finally, serum total IgE levels were negatively correlated with serum IL-10 levels in both breastfed and non-breastfed children with CMPA-related AEDS (p<0.001). We reported that exclusive breast-feeding induces hyposensitization in children with CMPA-related AEDS and it is associated with minor disease severity and higher serum IL-10 levels, resulting as useful disease-monitor marker. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

    Science.gov (United States)

    Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

    2016-04-01

    Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2.

  4. [Role of IL-6 in the development and pathogenesis of CIA and EAE].

    Science.gov (United States)

    Fujimoto, Minoru; Serada, Satoshi; Naka, Tetsuji

    2008-04-01

    Interleukin (IL)-6 is a pleiotropic cytokine that has crucial roles in the regulation of immune response, inflammation and hematopoiesis. Recently, a new inflammatory helper T cell subset which produces IL-17A (IL-17), termed Th17 cells was identified and has been reported to be involved in the development and pathogenesis of collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which are known as the mouse model of rheumatoid arthritis and multiple sclerosis, respectively. It has been demonstrated that IL-6 together with TGF-beta induces the differentiation of Th17 cells from naive helper T cells in vitro. However, IL-6 independent pathway of Th17 differentiation has also been reported, suggesting that the role of IL-6 in vivo in these diseases remains unclear. With the treatment of anti-IL-6R antibody in CIA and EAE, we could suppress the differentiation of antigen specific Th17 cells and the onset of diseases. These results indicate that IL-6 is involved in the induction of Th17 cells in vivo, and anti-IL-6R antibody might be a promising therapy of Th17-mediated autoimmune diseases.

  5. Basophil-derived IL-6 regulates TH17 cell differentiation and CD4 T cell immunity

    Science.gov (United States)

    Yuk, Chae Min; Park, Hyeung Ju; Kwon, Bo-In; Lah, Sang Joon; Chang, Jun; Kim, Ji-Young; Lee, Kyung-Mi; Park, Su-Hyung; Hong, Seokchan; Lee, Seung-Hyo

    2017-01-01

    Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote TH17 cell differentiation. In the TH17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and TH17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of TH17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of TH17 cell differentiation, which is dependent on IL-6 secretion. PMID:28134325

  6. Identification of IL6 as a susceptibility gene for major depressive disorder.

    Science.gov (United States)

    Zhang, Chen; Wu, Zhiguo; Zhao, Guoqing; Wang, Fan; Fang, Yiru

    2016-08-09

    Our previous work implied that interleukin 6 (IL6) may be a biological marker for major depressive disorder (MDD). In this study, we performed a comprehensive genetic study to determine the association between the gene encoding IL6 (IL6) and MDD in Han Chinese. There were 50 drug-naïve MDD patients and 50 healthy controls undergoing an mRNA expression study. A sample of 772 patients with MDD and 759 healthy controls were used for genetic analysis. Next, we performed an eQTL analysis to identify whether risk SNP(s) is associated with IL6 expression in brain. Our results showed that patients with MDD have higher levels of IL6 than healthy controls (P = 0.008). The SNP rs1800797 has a significant association with MDD (P = 0.01) in a dominant model. The eQTL analysis showed a marginally significant association between the rs1800797 and IL6 expression in the frontal cortex (P = 0.087). Our preliminary findings are suggestive of an association between rs1800797 and the risk of MDD. Further investigations are required to evaluate this association in larger samples to increase statistical power, and to examine the correlation between rs1800797 and IL6 methylation patterns.

  7. [Value of IL-6 and IL-8 in the diagnosis of neonatal sepsis].

    Science.gov (United States)

    Zhao, Feng-Xia; Liu, Guang-Hui; Zhang, Jian

    2015-12-01

    To explore the significance of interleukin-6 (IL-6) and IL-8 in the diagnosis of neonatal sepsis. This was a prospective study conducted between August 2014 and February 2015. A total of 140 neonates who were suspected infectious were enrolled and classified into a sepsis group (n=49) and a local infection group (n=91). Sixty-one neonates who were non-infectious served as the control group. Serum levels of IL-6 and IL-8 were measured before treatment and 3 days after treatment. The value of serum IL-6 and IL-8 for the diagnosis of neonatal sepsis was assessed by receiver operating characteristic (ROC) curve analysis. Before treatment, serum levels of IL-6 and IL-8 in the sepsis group were higher than those in the local infection and control groups (Psepsis group remained higher than that in the local infection and control groups (Pneonatal sepsis were 87.8%, 79.6% and 81.6% respectively; when the cut-off value of serum IL-8 was 54 pg/mL, the sensitivity, specificity and accuracy of serum IL-6 for the diagnosis of neonatal sepsis were 77.6%, 63.8% and 67.2% respectively. With the combination of serum IL-6 and IL-8 levels, the sensitivity, specificity and accuracy for the diagnosis of neonatal sepsis were 71.4%, 86.2% and 82.6% respectively. IL-6 and IL-8 participate in the inflammatory response and the serum levels of both vary with the severity of infection. The diagnostic value of IL-6 for neonatal sepsis is higher than IL-8. The combined detection of serum levels IL-6 and IL-8 may increase the accuracy of diagnosis of neonatal sepsis.

  8. IL-6 and TNF-α in unmedicated adults with ADHD: Relationship to cortisol awakening response.

    Science.gov (United States)

    Corominas-Roso, M; Armario, A; Palomar, G; Corrales, M; Carrasco, J; Richarte, V; Ferrer, R; Casas, M; Ramos-Quiroga, J A

    2017-05-01

    There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-α between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-α and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-α between groups. Pearson correlations were used to study associations between IL-6, TNF-α, and CAR. There were no significant differences in serum IL-6 or TNF-α levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0.386, p=0.020), TNF-α (r=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between IL-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-α, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-α and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies.

  9. Japanese encephalitis virus infection decrease endogenous IL-10 production: correlation with microglial activation and neuronal death.

    Science.gov (United States)

    Swarup, Vivek; Ghosh, Joydeep; Duseja, Rachna; Ghosh, Soumya; Basu, Anirban

    2007-06-13

    The anti-inflammatory cytokine interleukin (IL)-10 is synthesized in the central nervous system (CNS) and acts to limit clinical symptoms of stroke, multiple sclerosis, Alzheimer's disease, meningitis, and the behavioral changes that occur during bacterial infections. Expression of IL-10 is critical during the course of most major diseases in the CNS and promotes survival of neurons and all glial cells in the brain by blocking the effects of proinflammatory cytokines and by promoting expression of cell survival signals. In order to assess functional importance of this cytokine in viral encephalitis we have exploited an experimental model of Japanese encephalitis (JE). We report for the first time that in Japanese encephalitis, there is a progressive decline in level of IL-10. The extent of progressive decrease in IL-10 level following viral infection is inversely proportional to the increase in the level of proinflammatory cytokines as well as negative consequences that follows viral infection.

  10. Polimorfismos en el gen promotor de IL-10 en una muestra de pacientes colombianos con lepra

    Directory of Open Access Journals (Sweden)

    Nora Cardona-Castro

    2012-03-01

    Conclusiones. El haplotipo que encontramos asociado con lepra, -1082A-819C-592C/-1082A-819C-592C, se ha relacionado con baja producción de IL-10. Funcionalmente, esta baja producción de IL-10 puede tener consecuencias en la respuesta inmunitaria, además de implicaciones clínicas. Se han reportado diferentes haplotipos de IL-10 como marcadores de vulnerabilidad y resistencia de lepra en otras poblaciones, lo cual sugiere que las diferencias en la distribución de diversos polimorfismos del gen de IL-10 entre grupos étnicos, es un factor importante al determinar la asociación entre enfermedad y genes.   DOI: http://dx.doi.org/10.7705/biomedica.v32i1.386

  11. Importance of IL-10 and IL-17 cytokines in human asthma as studied ...

    African Journals Online (AJOL)

    McRoy

    Importance of IL-10 and IL-17 cytokines in human asthma as studied by ELISPOT ... Detection of cytokines and other functional assays can be used to evaluate an immune ..... differentiate into memory cells with specific cytokine producing or ...

  12. The role of IL-10 in microbiome-associated immune modulation and disease tolerance.

    Science.gov (United States)

    Levast, Benoît; Li, Zhigang; Madrenas, Joaquín

    2015-10-01

    Current research on the microbiome of humans and other species is revealing a fundamental role for the interaction between the microbiota and the immune system in determining the health status of the host. In these studies, the cytokine interleukin-10 (IL-10) is emerging as an important player. We present here an overview of the developments in the field emphasizing how the microbiota composition and its interplay with immune cells affect the health of the host through changes in IL-10 production. In addition, we explore the function that IL-10-producing immune cells may have on the qualitative and quantitative changes in the microbiota and thus influence the balance between microbial commensalism and pathogenicity. In the last section of this review, we present a summary of the strategies that target IL-10 for therapeutic purposes using probiotics, purified proteins or biologicals.

  13. Correlation of chronic periodontitis in tropical area and IFN-γ, IL-10, IL-17 levels

    Institute of Scientific and Technical Information of China (English)

    Qi-Ya Fu; Li Zhang; Li Duan; Shi-Yun Qian; Hong-Xia Pang

    2013-01-01

    Objective: To evaluate the correlation of chronic periodontitis in tropical area and IFN-γ, IL-10 and IL-17 levels. Methods: One hundred and forty-eight patients and one hundred and thirty-two healthy control subjects were included in the study. Clinical parameters (PI, GI and PD) and GCF levels of IFN-γ, IL-10 and IL-17 were measured at baseline, week 8, week 16 and week 24 after mechanical removal of dental plaque. IFN-γ and IL-10 were determined with ELISA methods and IL-17 was determined with the cytometric bead array. Results: Removal of dental plaque resulted in improvement in all clinical parameters. Meanwhile, GCF IL-17 declined to control levels, while GCF IFN-γ and IL-10 levels remained unchanged. Conclusions: The decline of GCF IL-17 levels in patients with resolution of periodontitis suggests that IL-17 is involved in the periodontal inflammatory process.

  14. Effects of IL-10 haplotype and atomic bomb radiation exposure on gastric cancer risk.

    Science.gov (United States)

    Hayashi, Tomonori; Ito, Reiko; Cologne, John; Maki, Mayumi; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Hayashi, Ikue; Imai, Kazue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Fujiwara, Saeko; Akahoshi, Masazumi; Nakachi, Kei

    2013-07-01

    Gastric cancer (GC) is one of the cancers that reveal increased risk of mortality and incidence in atomic bomb survivors. The incidence of gastric cancer in the Life Span Study cohort of the Radiation Effects Research Foundation (RERF) increased with radiation dose (gender-averaged excess relative risk per Gy = 0.28) and remains high more than 65 years after exposure. To assess a possible role of gene-environment interaction, we examined the dose response for gastric cancer incidence based on immunosuppression-related IL-10 genotype, in a cohort study with 200 cancer cases (93 intestinal, 96 diffuse and 11 other types) among 4,690 atomic bomb survivors participating in an immunological substudy. Using a single haplotype block composed of four haplotype-tagging SNPs (comprising the major haplotype allele IL-10-ATTA and the minor haplotype allele IL-10-GGCG, which are categorized by IL-10 polymorphisms at -819A>G and -592T>G, +1177T>C and +1589A>G), multiplicative and additive models for joint effects of radiation and this IL-10 haplotyping were examined. The IL-10 minor haplotype allele(s) was a risk factor for intestinal type gastric cancer but not for diffuse type gastric cancer. Radiation was not associated with intestinal type gastric cancer. In diffuse type gastric cancer, the haplotype-specific excess relative risk (ERR) for radiation was statistically significant only in the major homozygote category of IL-10 (ERR = 0.46/Gy, P = 0.037), whereas estimated ERR for radiation with the minor IL-10 homozygotes was close to 0 and nonsignificant. Thus, the minor IL-10 haplotype might act to reduce the radiation related risk of diffuse-type gastric cancer. The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer. © 2013 by Radiation Research Society

  15. IL-6, but not TNF-α, increases plasma YKL-40 in human subjects

    DEFF Research Database (Denmark)

    Nielsen, Anders R; Plomgaard, Peter; Krabbe, Karen S

    2011-01-01

    Plasma levels of YKL-40 are elevated in patients with systemic infection, inflammatory disorders and cancer. Both monocytes/macrophages, neutrophils, and cancer cells have the capacity to produce YKL-40, but the regulation during the inflammatory response is unknown. To study the possible role...... of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-a in the regulation of YKL-40 plasma levels, we included healthy men, who received either recombinant human (rh)IL-6 (n=6), rhTNF-a (n=8) or vehicle (n=7) for 3h. The plasma levels of IL-6 and TNF-a reached ~ 150 and ~ 18 pg/ml, respectively, during...

  16. Identification of IL6 as a susceptibility gene for major depressive disorder

    OpenAIRE

    2016-01-01

    Our previous work implied that interleukin 6 (IL6) may be a biological marker for major depressive disorder (MDD). In this study, we performed a comprehensive genetic study to determine the association between the gene encoding IL6 (IL6) and MDD in Han Chinese. There were 50 drug-naïve MDD patients and 50 healthy controls undergoing an mRNA expression study. A sample of 772 patients with MDD and 759 healthy controls were used for genetic analysis. Next, we performed an eQTL analysis to identi...

  17. Long-term vitamin D3 supplementation does not prevent colonic inflammation or modulate bone health in IL-10 knockout mice at young adulthood.

    Science.gov (United States)

    Glenn, Andrea J; Fielding, Kristina A; Chen, Jianmin; Comelli, Elena M; Ward, Wendy E

    2014-09-22

    Inflammatory bowel disease (IBD) is an idiopathic disease that can impair bone metabolism. Low vitamin D status has been implicated in its progress. This study used interleukin (IL)-10 knockout (KO) mice, that develop an intestinal inflammation when housed in a non-sterile environment, to determine if supplementation with vitamin D3 throughout life could mitigate inflammation and attenuate the lower bone mineral content (BMC) and density (BMD), and bone strength. Female IL-10 KO mice were randomized 25 or 5000 IU vitamin D3/kg diet throughout pregnancy and lactation. At weaning, offspring received the same or opposite diet as their mother until age three months. Body weight growth was similar among groups within a sex. At three months of age, there were no differences in inflammation and gene expression in the colon of offspring. Male offspring exposed to continuous 25 IU vitamin D3/kg diet had lower (p vitamin D3 until weaning had higher serum IL-6. There were no differences in femur or vertebral BMC, BMD or bone strength. In summary, long-term exposure to vitamin D3 did not attenuate intestinal inflammation or preserve bone mineral or bone strength. Thus, supplementation with vitamin D3 does not exert anti-inflammatory effects in this mouse model that mimics human inflammatory bowel disease.

  18. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    Science.gov (United States)

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients.

  19. Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis.

    Science.gov (United States)

    Zhou, Kai; Zhong, Qi; Wang, Yan-Chun; Xiong, Xiao-Yi; Meng, Zhao-You; Zhao, Ting; Zhu, Wen-Yao; Liao, Mao-Fan; Wu, Li-Rong; Yang, Yuan-Rui; Liu, Juan; Duan, Chun-Mei; Li, Jie; Gong, Qiu-Wen; Liu, Liang; Yang, Mei-Hua; Xiong, Ao; Wang, Jian; Yang, Qing-Wu

    2017-03-01

    Inflammation mediated by the peripheral infiltration of inflammatory cells plays an important role in intracerebral hemorrhage (ICH) induced secondary injury. Previous studies have indicated that regulatory T lymphocytes (Tregs) might reduce ICH-induced inflammation, but the precise mechanisms that contribute to ICH-induced inflammatory injury remain unclear. Our results show that the number of Tregs in the brain increases after ICH. Inducing Tregs deletion using a CD25 antibody or Foxp3(DTR)-mice increased neurological deficient scores (NDS), the level of inflammatory factors, hematoma volumes, and neuronal degeneration. Meanwhile, boosting Tregs using a CD28 super-agonist antibody reduced the inflammatory injury. Furthermore, Tregs depletion shifted microglia/macrophage polarization toward the M1 phenotype while boosting Tregs shifted this transition toward the M2 phenotype. In vitro, a transwell co-culture model of microglia and Tregs indicated that Tregs changed the polarization of microglia, decreased the expression of MHC-II, IL-6, and TNF-α and increased CD206 expression. IL-10 originating from Tregs mediated the microglia polarization by increasing the expression of Glycogen Synthase Kinase 3 beta (GSK3β), which phosphorylates and inactivates Phosphatase and Tensin homologue (PTEN) in microglia, TGF-β did not participate in this conversion. Thus, Tregs ameliorated ICH-induced inflammatory injury by modulating microglia/macrophage polarization toward the M2 phenotype through the IL-10/GSK3β/PTEN axis.

  20. Cytokine serum profiles in allergic and non-allergic asthma. Increased production of IL-10 by non-allergic asthmatic patients.

    Science.gov (United States)

    Sánchez-Guerrero, I; Vegara, R P; Herrero, N; García-Alonso, A M; Luna, A; Alvarez, M R

    1997-01-01

    Studies were undertaken to determine whether differences in serum cytokine balances could be involved in the pathogenesis of allergic and in non-allergic asthma. At this propose, interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, interleukin-6, and interleukin-10 were measured by enzimoimmunoassay. The analysis was performed on 24 allergic and 24 non-allergic asthmatic patients and 16 healthy subjects. IFN-gamma and TNF-alpha, included into the type 1 cytokines, appeared significantly increased in the allergic with respect to the non-allergic asthmatic patients (p = 0.01) and (p < 0.001) respectively, while IL-10, which belongs to the type 2 cytokines, was significantly increased in the non-allergic asthmatic (p < 0.001). The IL-6 analysis did not show any significant difference in either of the study group. The most interesting finding was the high serum IL-10 values detected in intrinsic asthmatic patients, which in turn, suggests that this cytokine could participate in the regulation of different immunological features that occurs in non-allergic asthma, and maybe it could indicate a higher stimulated state of cells in this type of asthma. The data presented in this report show a different cytokine profile in serum from allergic and non-allergic asthmatic patients and denote a stronger prevalence of type 2 cytokines in intrinsic asthma.

  1. Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus

    Science.gov (United States)

    Godsell, Jack; Rudloff, Ina; Kandane-Rathnayake, Rangi; Hoi, Alberta; Nold, Marcel F.; Morand, Eric F.; Harris, James

    2016-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the development of autoantibodies to nuclear antigens and inflammatory responses mediated by multiple cytokines. Although previous studies have determined clinical associations between SLE and the anti-inflammatory cytokines IL-10 and IL-37, their role in the disease, or their potential as biomarkers, remains unclear. We examined serum levels of IL-10 and IL-37 in a large cohort of SLE patients, with detailed longitudinal clinical data. We demonstrate a statistically significant association of serum IL-10 with disease activity, with higher levels in active compared to inactive disease. High first visit IL-10 was predictive of high subsequent disease activity; patients with IL-10 in highest quartile at first visit were 3.6 times more likely to have active disease in subsequent visits. Serum IL-37 was also higher in SLE patients compared to control, and was strongly associated with Asian ethnicity. However, IL-37 was not statistically significantly associated with disease activity. IL-37 was significantly reduced in patients with organ damage but this association was attenuated in multivariable analysis. The data suggest that IL-10, but not IL-37, may have potential as a biomarker predictive for disease activity in SLE. PMID:27708376

  2. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

    Science.gov (United States)

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Muller, Werner; Cretney, Erika; Nutt, Stephen L.; Smyth, Mark J.; Haque, Ashraful; Hill, Geoffrey R.; Sundar, Shyam; Kallies, Axel; Engwerda, Christian R.

    2016-01-01

    Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. PMID:26765224

  3. IL-10 -592A/C polymorphism is associated with severity of Hashimoto's disease.

    Science.gov (United States)

    Inoue, Naoya; Watanabe, Mikio; Wada, Megumi; Morita, Mami; Hidaka, Yoh; Iwatani, Yoshinori

    2013-10-01

    The genetic producibilities of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines are associated with the prognosis of autoimmune thyroid diseases (AITDs). Interleukin (IL)-10 is considered to be a Th2 cytokine that can exhibit an anti-inflammatory role. Furthermore, IL-10 may be associated with the development of IgG4-related diseases, because IL-10 promotes IgG4 production by B cells. To evaluate the relationship between the functional -592 A/C polymorphism in the gene encoding IL-10 and the prognosis of AITDs, we genotyped this polymorphism in 57 patients with intractable GD, 43 patients with GD in remission, 63 patients with severe HD, 44 patients with untreated mild HD, and 62 healthy volunteers by the direct sequencing method. The CC genotype, which is associated with higher producibility of IL-10, was more frequent in patients with severe HD than in those with mild HD (p=0.0201). However, there were no significant differences in serum IgG4 levels between these two groups of HD patients or among 3 genotypes of this polymorphism. There were no significant differences in genotype and allele frequencies between the two GD groups, or between the controls and AITD patients. These data indicate that the functional -592 A/C polymorphism in the IL10 gene is associated with the severity of HD but not with serum IgG4 levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.

    Science.gov (United States)

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H; Sheel, Meru; Faleiro, Rebecca J; Bunn, Patrick T; Best, Shannon E; Beattie, Lynette; Ng, Susanna S; Edwards, Chelsea L; Muller, Werner; Cretney, Erika; Nutt, Stephen L; Smyth, Mark J; Haque, Ashraful; Hill, Geoffrey R; Sundar, Shyam; Kallies, Axel; Engwerda, Christian R

    2016-01-01

    Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.

  5. Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential

    Science.gov (United States)

    Nagpal, Gandharva; Usmani, Salman Sadullah; Dhanda, Sandeep Kumar; Kaur, Harpreet; Singh, Sandeep; Sharma, Meenu; Raghava, Gajendra P. S.

    2017-01-01

    In the past, numerous methods have been developed to predict MHC class II binders or T-helper epitopes for designing the epitope-based vaccines against pathogens. In contrast, limited attempts have been made to develop methods for predicting T-helper epitopes/peptides that can induce a specific type of cytokine. This paper describes a method, developed for predicting interleukin-10 (IL-10) inducing peptides, a cytokine responsible for suppressing the immune system. All models were trained and tested on experimentally validated 394 IL-10 inducing and 848 non-inducing peptides. It was observed that certain types of residues and motifs are more frequent in IL-10 inducing peptides than in non-inducing peptides. Based on this analysis, we developed composition-based models using various machine-learning techniques. Random Forest-based model achieved the maximum Matthews’s Correlation Coefficient (MCC) value of 0.59 with an accuracy of 81.24% developed using dipeptide composition. In order to facilitate the community, we developed a web server “IL-10pred”, standalone packages and a mobile app for designing IL-10 inducing peptides (http://crdd.osdd.net/raghava/IL-10pred/). PMID:28211521

  6. Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex

    Science.gov (United States)

    Lupardus, Patrick J.; Skiniotis, Georgios; Rice, Amanda J.; Thomas, Christoph; Fischer, Suzanne; Walz, Thomas; Garcia, K. Christopher

    2011-01-01

    Summary The shared cytokine receptor gp130 signals as a homodimer or heterodimer through activation of Janus kinases (Jaks) associated with the receptor intracellular domains. Here we reconstitute, in parts and whole, the full-length gp130 homodimer in complex with the cytokine interleukin-6 (IL-6), its alpha receptor (IL-6Rα) and Jak1, for electron microscopy imaging. We find that the full-length gp130 homodimer complex has intimate interactions between the trans- and juxtamembrane segments of the two receptors, appearing to rigidify the connection between the extra- and intracellular regions. 2D averages and 3D reconstructions of full-length Jak1 reveal a three-lobed structure comprised of FERM-SH2, pseudokinase and kinase modules possessing extensive inter-segmental flexibility that likely facilitates allosteric activation. Single-particle imaging of the gp130/IL-6/IL-6Rα/Jak1 holocomplex shows Jak1 associated with the membrane proximal intracellular regions of gp130, abutting the would-be inner leaflet of the cell membrane. Jak1 association with gp130 is enhanced by the presence of a membrane environment. PMID:21220115

  7. IL-10 deficiency exacerbates the brain inflammatory response to permanent ischemia without preventing resolution of the lesion

    Science.gov (United States)

    Pérez-de Puig, Isabel; Miró, Francesc; Salas-Perdomo, Angélica; Bonfill-Teixidor, Ester; Ferrer-Ferrer, Maura; Márquez-Kisinousky, Leonardo; Planas, Anna M

    2013-01-01

    Stroke induces inflammation that can aggravate brain damage. This work examines whether interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of permanent middle cerebral artery occlusion (pMCAO). Expression of IL-10 and IL-10 receptor (IL-10R) increased after ischemia. From day 4, reactive astrocytes showed strong IL-10R immunoreactivity. Interleukin-10 knockout (IL-10 KO) mice kept in conventional housing showed more mortality after pMCAO than the wild type (WT). This effect was associated with the presence of signs of colitis in the IL-10 KO mice, suggesting that ongoing systemic inflammation was a confounding factor. In a pathogen-free environment, IL-10 deficiency slightly increased infarct volume and neurologic deficits. Induction of proinflammatory molecules in the IL-10 KO brain was similar to that in the WT 6 hours after ischemia, but was higher at day 4, while differences decreased at day 7. Deficiency of IL-10 promoted the presence of more mature phagocytic cells in the ischemic tissue, and enhanced the expression of M2 markers and the T-cell inhibitory molecule CTLA-4. These findings agree with a role of IL-10 in attenuating local inflammatory reactions, but do not support an essential function of IL-10 in lesion resolution. Upregulation of alternative immunosuppressive molecules after brain ischemia can compensate, at least in part, the absence of IL-10. PMID:24022622

  8. 小分子IL-6/STAT3信号通路抑制剂%Small Molecule Inhibitors of IL-6/STAT3 Signaling

    Institute of Scientific and Technical Information of China (English)

    叶霁青; 岳晓虹; 孙丽萍

    2016-01-01

    IL-6 is a widespread cytokine which participates in many biological responses.All members of the IL-6 cytokine family are able to activate STAT3,and STAT3 is also recognized as the main mediator of IL-6 functions.IL-6 binding to cell surface receptors results in the activation of the Janus kinases(JAKs) which cause STAT3 phosphorylated.Then activated STAT3 dimerizes translocates to the nucleus and combines with target genes with specific sites,then activats DNA transcriptional activity.Studies show that the abnormally activated STAT3 in cells plays an important role in tumorigenesis and malignant transformation.Meanwhile,STAT3 is a valid target for novel anticancer drug design.So far,many methods,such as structure-based virtual screening,high throughput screening,fragment-based drug design,have been used to screen and design novel STAT3 inhibitors,and thus several classes of small molecule compounds have been identified as STAT3 inhibitors.In this review,we mainly focus on the small molecule IL-6/STAT3 inhibitors especially target STAT3 protein which have been optimized and identified since 2013.%IL-6是细胞内广泛存在的一种细胞因子,参与细胞内大量的生物应答.研究表明所有IL-6家族的细胞因子均能激活STAT3蛋白,同时,STAT3被认为是介导IL-6功能的主要因子.IL-6与其受体结合,激活JAKs,从而使STAT3磷酸化激活,活化的STAT3二聚化,向细胞核内转移并与其靶基因特定位点结合从而调节基因的转录活性.大量的证据表明细胞中异常活化的STAT3在肿瘤生成与恶性转化中具有重要作用.研究显示STAT3蛋白也是抗肿瘤药物设计的有效靶点.到目前为止,多种药物设计方法,如基于结构的虚拟筛选、高通量筛选、基于片段的药物设计等被用于STAT3抑制剂的筛选以及设计;文献也已经报道了许多具有抗肿瘤活性的STAT3抑制剂.本文主要介绍了近年来小分子IL-6/STAT3信号通路

  9. Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1.

    Science.gov (United States)

    Quante, Timo; Ng, Yee Ching; Ramsay, Emma E; Henness, Sheridan; Allen, Jodi C; Parmentier, Johannes; Ge, Qi; Ammit, Alaina J

    2008-08-01

    The mechanisms by which corticosteroids reduce airway inflammation are not completely understood. Traditionally, corticosteroids were thought to inhibit cytokines exclusively at the transcriptional level. Our recent evidence, obtained in airway smooth muscle (ASM), no longer supports this view. We have found that corticosteroids do not act at the transcriptional level to reduce TNF-alpha-induced IL-6 gene expression. Rather, corticosteroids inhibit TNF-alpha-induced IL-6 secretion by reducing the stability of the IL-6 mRNA transcript. TNF-alpha-induced IL-6 mRNA decays at a significantly faster rate in ASM cells pretreated with the corticosteroid dexamethasone (t(1/2) = 2.4 h), compared to vehicle (t(1/2) = 9.0 h; P ASM cells.

  10. Hyper-inflammation and skin destruction mediated by rosiglitazone activation of macrophages in IL-6 deficiency

    DEFF Research Database (Denmark)

    Das, Lopa M; Rosenjack, Julie; Au, Liemin;

    2015-01-01

    Injury initiates recruitment of macrophages to support tissue repair; however, excessive macrophage activity may exacerbate tissue damage causing further destruction and subsequent delay in wound repair. Here we show that the peroxisome proliferation-activated receptor-γ agonist, rosiglitazone......-antibodies against IL-6, mimicking IL-6 deficiency in human diseases. IL-6 deficiency when combined with Rosi-mediated upregulation of suppressor of cytokine signaling 3 leads to an altered ratio of nuclear signal transducer and activator of transcription 3/NF-κB that allows hyper-induction of inducible nitric oxide...... synthase (iNOS). Macrophages activated in this manner cause de novo tissue destruction, recapitulating human chronic wounds, and can be reversed in vivo by recombinant IL-6, blocking macrophage infiltration, or neutralizing iNOS. This study provides insight into an unanticipated paradoxical role of Rosi...

  11. THE CHANGES OF IL-1β AND IL-6 LEVEL AT DIFFERENT ALTITUDE AND THEIR SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    Jia Mian; Geng Paili; Zhu Haihong; Wu Hongfu

    2006-01-01

    Objective To investigate the changes of the concentration of interkeukine β 1(IL-1β) and Interleukine 6(IL-6) in the serum of the people who live in the different altitude, and try to find the relation between the cytokines (CK) and the hypoxia adaptation and some diseases caused by hypoxia. Methods Using enzyme linked immunoabsorbent assay (ELISA) to detect the level of the concentration of IL-1β and IL-6 in the serum. Results The concentration of IL-1β showed significant increase in values (P<0.05) at 4050m. IL-6 in same altitude showed obvious changes as well (P<0.05). Conclusion The results showed that the concentration of IL-1β and IL-6 have significant changes in the serum. This means that they may be involved in the process of the adaptation and some sickness because of hypoxia.

  12. Interleukin 6 (IL6) as a predictor outcome in patients with ...

    African Journals Online (AJOL)

    Elham Ragab

    2012-05-15

    May 15, 2012 ... stay, blood loss, recovery time (return to work), and liver function tests were documented. IL-6 was ... treated, with individuals infected with the more resilient geno- type-1 ... This lesser degree of operative stress was also con-.

  13. IL-6 regulates exercise and training-induced adaptations in subcutaneous adipose tissue in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Jakobsen, Anne Hviid; Hassing, Helle Adser

    2012-01-01

    Aim: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. Methods: Four months old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1h of treadmill exercise, where subcutaneous...... adipose tissue (AT) was removed either immediately after, 4h or 10h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. Results: AT leptin mRNA decreased immediately after a single running exercise bout in both...... in regulating exercise and training-induced leptin and PPAR¿ expression in adipose tissue. In addition, while IL-6 is required for TNF-a mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue....

  14. Comparison of the G-174C polymorphism of interleukin (IL)-6 in ...

    African Journals Online (AJOL)

    enoh

    2012-04-05

    Apr 5, 2012 ... binding site for the transcription factor NF-1, resulting in repressed ... leukocyte pellet using a DNA extraction kit (AXYGEN, California,. USA). .... S, Woo P (1998) The effect of novel polymorphisms in the interleukin-. 6 (IL-6) ...

  15. Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

    DEFF Research Database (Denmark)

    Teilmann, Anne Charlotte; Rozell, Björn; Kalliokoski, Otto

    2016-01-01

    Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cyt......Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels...... of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands......, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing...

  16. (-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Bao-He Zhu; Hua-Yun Chen; Wen-Hua Zhan; Cheng-You Wang; Shi-Rong Cai; Zhao Wang; Chang-Hua Zhang; Yu-Long He

    2011-01-01

    AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer.METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditioned medium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR).Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay.RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490,VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited

  17. IL-10-overexpressing B cells regulate innate and adaptive immune responses.

    Science.gov (United States)

    Stanic, Barbara; van de Veen, Willem; Wirz, Oliver F; Rückert, Beate; Morita, Hideaki; Söllner, Stefan; Akdis, Cezmi A; Akdis, Mübeccel

    2015-03-01

    Distinct human IL-10-producing B-cell subsets with immunoregulatory properties have been described. However, the broader spectrum of their direct cellular targets and suppressive mechanisms has not been extensively studied, particularly in relation to direct and indirect IL-10-mediated functions. The aim of the study was to investigate the effects of IL-10 overexpression on the phenotype and immunoregulatory capacity of B cells. Primary human B cells were transfected with hIL-10, and IL-10-overexpressing B cells were characterized for cytokine and immunoglobulin production by means of specific ELISA and bead-based assays. Antigen presentation, costimulation capacity, and transcription factor signatures were analyzed by means of flow cytometry and quantitative RT-PCR. Effects of IL-10-overexpresing B cells on Toll-like receptor-triggered cytokine release from PBMCs, LPS-triggered maturation of monocyte-derived dendritic cells, and tetanus toxoid-induced PBMC proliferation were assessed in autologous cocultures. IL-10-overexpressing B cells acquired a prominent immunoregulatory profile comprising upregulation of suppressor of cytokine signaling 3 (SOCS3), glycoprotein A repetitions predominant (GARP), the IL-2 receptor α chain (CD25), and programmed cell death 1 ligand 1 (PD-L1). Concurrently, their secretion profile was characterized by a significant reduction in levels of proinflammatory cytokines (TNF-α, IL-8, and macrophage inflammatory protein 1α) and augmented production of anti-inflammatory IL-1 receptor antagonist and vascular endothelial growth factor. Furthermore, IL-10 overexpression was associated with a decrease in costimulatory potential. IL-10-overexpressing B cells secreted less IgE and potently suppressed proinflammatory cytokines in PBMCs, maturation of monocyte-derived dendritic cells (rendering their profile to regulatory phenotype), and antigen-specific proliferation in vitro. Our data demonstrate an essential role for IL-10 in inducing an

  18. CYLD enhances severe listeriosis by impairing IL-6/STAT3-dependent fibrin production.

    Directory of Open Access Journals (Sweden)

    Gopala Nishanth

    Full Text Available The facultative intracellular bacterium Listeria monocytogenes (Lm may cause severe infection in humans and livestock. Control of acute listeriosis is primarily dependent on innate immune responses, which are strongly regulated by NF-κB, and tissue protective factors including fibrin. However, molecular pathways connecting NF-κB and fibrin production are poorly described. Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-κB-dependent immune responses, regulated these protective host responses in murine listeriosis. Upon high dose systemic infection, all C57BL/6 Cyld(-/- mice survived, whereas 100% of wildtype mice succumbed due to severe liver pathology with impaired pathogen control and hemorrhage within 6 days. Upon in vitro infection with Lm, CYLD reduced NF-κB-dependent production of reactive oxygen species, interleukin (IL-6 secretion, and control of bacteria in macrophages. Furthermore, Western blot analyses showed that CYLD impaired STAT3-dependent fibrin production in cultivated hepatocytes. Immunoprecipitation experiments revealed that CYLD interacted with STAT3 in the cytoplasm and strongly reduced K63-ubiquitination of STAT3 in IL-6 stimulated hepatocytes. In addition, CYLD diminished IL-6-induced STAT3 activity by reducing nuclear accumulation of phosphorylated STAT3. In vivo, CYLD also reduced hepatic STAT3 K63-ubiquitination and activation, NF-κB activation, IL-6 and NOX2 mRNA production as well as fibrin production in murine listeriosis. In vivo neutralization of IL-6 by anti-IL-6 antibody, STAT3 by siRNA, and fibrin by warfarin treatment, respectively, demonstrated that IL-6-induced, STAT3-mediated fibrin production significantly contributed to protection in Cyld(-/- mice. In addition, in vivo Cyld siRNA treatment increased STAT3 phosphorylation, fibrin production, pathogen control and survival of Lm-infected WT mice illustrating that therapeutic inhibition of CYLD augments the

  19. CYLD enhances severe listeriosis by impairing IL-6/STAT3-dependent fibrin production.

    Science.gov (United States)

    Nishanth, Gopala; Deckert, Martina; Wex, Katharina; Massoumi, Ramin; Schweitzer, Katrin; Naumann, Michael; Schlüter, Dirk

    2013-01-01

    The facultative intracellular bacterium Listeria monocytogenes (Lm) may cause severe infection in humans and livestock. Control of acute listeriosis is primarily dependent on innate immune responses, which are strongly regulated by NF-κB, and tissue protective factors including fibrin. However, molecular pathways connecting NF-κB and fibrin production are poorly described. Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-κB-dependent immune responses, regulated these protective host responses in murine listeriosis. Upon high dose systemic infection, all C57BL/6 Cyld(-/-) mice survived, whereas 100% of wildtype mice succumbed due to severe liver pathology with impaired pathogen control and hemorrhage within 6 days. Upon in vitro infection with Lm, CYLD reduced NF-κB-dependent production of reactive oxygen species, interleukin (IL)-6 secretion, and control of bacteria in macrophages. Furthermore, Western blot analyses showed that CYLD impaired STAT3-dependent fibrin production in cultivated hepatocytes. Immunoprecipitation experiments revealed that CYLD interacted with STAT3 in the cytoplasm and strongly reduced K63-ubiquitination of STAT3 in IL-6 stimulated hepatocytes. In addition, CYLD diminished IL-6-induced STAT3 activity by reducing nuclear accumulation of phosphorylated STAT3. In vivo, CYLD also reduced hepatic STAT3 K63-ubiquitination and activation, NF-κB activation, IL-6 and NOX2 mRNA production as well as fibrin production in murine listeriosis. In vivo neutralization of IL-6 by anti-IL-6 antibody, STAT3 by siRNA, and fibrin by warfarin treatment, respectively, demonstrated that IL-6-induced, STAT3-mediated fibrin production significantly contributed to protection in Cyld(-/-) mice. In addition, in vivo Cyld siRNA treatment increased STAT3 phosphorylation, fibrin production, pathogen control and survival of Lm-infected WT mice illustrating that therapeutic inhibition of CYLD augments the protective NF-κB/IL

  20. Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

    OpenAIRE

    2015-01-01

    Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high...

  1. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  2. Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures.

    Science.gov (United States)

    Loppnow, Harald; Zhang, Li; Buerke, Michael; Lautenschläger, Michael; Chen, Li; Frister, Adrian; Schlitt, Axel; Luther, Tanja; Song, Nan; Hofmann, Britt; Rose-John, Stefan; Silber, Rolf-Edgar; Müller-Werdan, Ursula; Werdan, Karl

    2011-04-01

    Inflammatory pathways are involved in the development of atherosclerosis. Interaction of vessel wall cells and invading monocytes by cytokines may trigger local inflammatory processes. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are standard medications used in cardiovascular diseases. They are thought to have anti-inflammatory capacities, in addition to their lipid-lowering effects. We investigated the anti-inflammatory effect of statins in the cytokine-mediated-interaction-model of human vascular smooth muscle cells (SMC) and human mononuclear cells (MNC). In this atherosclerosis-related inflammatory model LPS (lipopolysaccharide, endotoxin), as well as high mobility group box 1 stimulation resulted in synergistic (i.e. over-additive) IL-6 (interleukin-6) production as measured in ELISA. Recombinant IL-1, tumour necrosis factor-α and IL-6 mediated the synergistic IL-6 production. The standard anti-inflammatory drugs aspirin and indomethacin (Indo) reduced the synergistic IL-6 production by 60%. Simvastatin, atorvastatin, fluvastatin or pravastatin reduced the IL-6 production by 53%, 50%, 64% and 60%, respectively. The inhibition by the statins was dose dependent. Combination of statins with aspirin and/or Indo resulted in complete inhibition of the synergistic IL-6 production. The same inhibitors blocked STAT3 phosphorylation, providing evidence for an autocrine role of IL-6 in the synergism. MNC from volunteers after 5 day aspirin or simvastatin administration showed no decreased IL-6 production, probably due to drug removal during MNC isolation. Taken together, the data show that anti-inflammatory functions (here shown for statins) can be sensitively and reproducibly determined in this novel SMC/MNC coculture model. These data implicate that statins have the capacity to affect atherosclerosis by regulating cytokine-mediated innate inflammatory pathways in the vessel wall.

  3. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells.

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-12-15

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC.

  4. Efficacy of hemofiltration with PEPA membrane for IL-6 removal in a rat sepsis model.

    Science.gov (United States)

    Maeda, Hayata; Tomisawa, Narumi; Jimbo, Yoichi; Harii, Norikazu; Matsuda, Kenichi

    2017-09-11

    Recently, intensive care physicians have focused on continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of sepsis. We aimed to establish extracorporeal circulation in a rat sepsis model to evaluate the cytokine removal properties of mini-modules using two types of membrane materials. Rats were divided into polyester polymer alloy (PEPA) and cellulose triacetate (CTA) groups as membrane materials of mini-modules. One hour after 0.1 mg/kg of lipopolysaccharide administration, continuous hemofiltration (CHF) was started in each group. Plasma interleukin-6 (IL-6), an important mediator of sepsis, was measured over time during hemofiltration. The peak IL-6 concentration in PEPA group was approximately 13,000 pg/mL, in comparison to approximately 31,000 pg/mL in CTA group. IL-6 clearance in PEPA group was much more than CTA group. Since IL-6 was not detected in the filtrate in PEPA group, it was considered that IL-6 was adsorbed to the membrane. In conclusion, our results suggest that CHF with PEPA hemofilter can be suitable for removing IL-6 from the blood stream efficiently.

  5. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans

    DEFF Research Database (Denmark)

    Starkie, Rebecca; Ostrowski, Sisse Rye; Jauffred, Sune

    2003-01-01

    During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance and athero......During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance...... and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli...... exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced...

  6. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

    Science.gov (United States)

    Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

    2010-01-01

    Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

  7. Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil.

    Science.gov (United States)

    da Silva, Naylê Maria Oliveira; Germano, Fabiana Nunes; Vidales-Braz, Beatris Maria; Carmo Zanella, Ricardo do; dos Santos, Deise Machado; Lobato, Rubens; de Martinez, Ana Maria Barral

    2015-06-01

    Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p=0.005 and p=0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p<0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p=0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).

  8. Relation cellular- molecular between serum IL10 levels and hyperalgesia variation in adjuvant- induced arthritis

    Directory of Open Access Journals (Sweden)

    Zenab Akhtari

    2015-01-01

    Full Text Available Background: Regarding to the important anti-inflammatory role of IL10 during inflammation process and hyperalgesia and edema variation during CFA-induced arthritis and also the increase of Spinal mu opioid receptor (mOR expression, in this study researchers investigate the role of serum IL10 level on mOR expression and edema and hyperalgesia variation during different stages of Complete Freund`s Adjuvant (CFA - induced arthritis in male Wistar rats. Materials and Methods: Mono-arthritis was induced by CFA and inflammatory symptoms (hyperalgesia and edema were assessed on 0, 3, 7, 14th and 21st days of study. Anti-IL10 was administered during the 21 days of study in different experimental groups. mOR expression were detected by western blotting on 0, 3,7, 14th and 21st days of study. Data was analyzed by SPSS statistical software version 19 with using one way ANOVA (post hoc Tokey's. Results: Our results showed that anti-IL10 administration in AA group (Adjuvant Arthritis caused an increase in the paw volume and hyperalgesia until 21st of study. Our study stated that there were no significant differences in spinal mOR expression between AA and AA+anti-IL10rats. Conclusion: Our study confirmed that anti-IL10administration caused to hyperalgesia and edema during AA inflammation. Also these findings suggested that mOR expression increased in chronic phase of AA inflammation, however an increase in the level of spinal mu opioid receptor (mOR expression during AA inflammation is not mediated directly via the effect of serum IL-10.

  9. A Study on the Effects of IL-10 in Anti-Thy 1-Induced Glomerulonephritis in Rats

    NARCIS (Netherlands)

    Rachmawati, H.; Beljaars, L.; Reker-Smit, C.; Bakker, H. I.; Van Loenen-Weemaes, A. M.; Poelstra, K.

    2009-01-01

    In the present study, we examined the effects of IL-10 after 24 h in a model of acute glomerulonephritis (GN). One hour after the anti-Thy I antibody administration, a single i.v. dose of IL-10 was administered to rats. Normal rats, control nephritic rats and nephritic rats treated with IL-10, were

  10. Structural characterization and immunomodulatory effects of polysaccharides from Phellinus linteus and Phellinus igniarius on the IL-6/IL-10 cytokine balance of the mouse macrophage cell lines (RAW 264.7)

    NARCIS (Netherlands)

    Suabjakyong, Papawee; Nishimura, Kazuhiro; Toida, Toshihiko; Griensven, Van L.J.L.D.

    2015-01-01

    Phellinus linteus and igniarius (L.) Quel. have been used in traditional Asian medicine for over two centuries against a variety of diseases. Polysaccharides from their fruiting bodies show strong immunomodulatory activity. In this study we characterized the structure and composition of polysacch

  11. THE INFLUENCE OF POLYMORPHISM IN THE INFLAMMATORY GENES IL-1, ß IL-6, IL-10, PPAR?2 AND COX-2 IN PATIENTS WITH MULTIPLE MYELOMA UNDERGOING AUTOLOGOUS BONE MARROW TRANSPLANTATION

    DEFF Research Database (Denmark)

    Vangsted, Annette; Klausen, Tobias W.; Gimsing, Peter;

    2007-01-01

    in genes involved in the inflammatory response in 348 patients undergoing high dose treatment followed by autologous tem cell transplantation. We found that the polymorphism in IL-1ß T-31C significantly influence overall survival (p=0.02). Homozygous carriers of the variant C-allele had a significantly...

  12. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle.

    Science.gov (United States)

    Dagdeviren, Sezin; Jung, Dae Young; Friedline, Randall H; Noh, Hye Lim; Kim, Jong Hun; Patel, Payal R; Tsitsilianos, Nicholas; Inashima, Kunikazu; Tran, Duy A; Hu, Xiaodi; Loubato, Marilia M; Craige, Siobhan M; Kwon, Jung Yeon; Lee, Ki Won; Kim, Jason K

    2017-02-01

    Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (M(IL10)) and in wild-type mice during hyperinsulinemic-euglycemic clamping. Despite similar fat mass and energy balance, M(IL10) mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (∼60%; P age-matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging M(IL10) mice. These results demonstrate the importance of skeletal muscle inflammation in aging-mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti-inflammatory cytokine in the treatment of aging-mediated insulin resistance.-Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. © FASEB.

  13. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway.

    Science.gov (United States)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-07-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell differentiation in mice. Using in vitro co-culture systems and subsequent cytokine analysis, we showed that LSECs induced high amounts of the anti-inflammatory cytokine IL-10 in developing Th1 cells. These LSEC-stimulated Th1 cells had no pro-inflammatory capacity in vivo but instead actively suppressed an inflammatory Th1-cell-induced delayed-type hypersensitivity reaction. Blockage of IL-10 signaling in vivo inhibited immunosuppressive activity of LSEC-stimulated Th1 cells. We identified the Notch pathway as a mechanism how LSECs trigger IL-10 expression in Th1 cells. LSECs expressed high levels of the Delta-like and Jagged family of Notch ligands and induced expression of the Notch target genes hes-1 and deltex-1 in Th1 cells. Blockade of Notch signaling selectively inhibited IL-10 induction in Th1 cells by LSECs. Our findings suggest that LSEC-induced IL-10 expression in Th1 cells via the Notch pathway may contribute to the control of hepatic inflammatory immune responses by induction of a self-regulatory mechanism in pro-inflammatory Th1 cells.

  14. Serum Levels of IL-10 and IL-22 Cytokines in Patients with Psoriasis.

    Science.gov (United States)

    Sobhan, Mohammad Reza; Farshchian, Mahmood; Hoseinzadeh, Ali; Ghasemibasir, Hamid Reza; Solgi, Ghasem

    2016-12-01

    As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-10 and IL-22 have not been sufficiently investigated. To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. A total of 28 patients with psoriasis were compared with 28 age and sex-matched healthy subjects. Psoriasis Area and Severity Index (PASI) criteria were used to measure the severity of the disease. Serum levels of IL-10 and IL-22 were measured in both groups and compared. The mean serum level of IL-10 was 89.5±18.7 in patients compared to 117.2±23.4 pg/ml in the controls (p=0.36). Also, serum level of IL-22 was 284.1±49.7 in patients versus 425.4±82.8 pg/ml in control group (p=0.17). There was a significant direct correlation between levels of IL-10 and IL-22 in patients group (p=0.0005). The clinical severity of psoriasis was significantly correlated with high levels of IL-22 (ppsoriasis.

  15. Glutamate decreases the secretion of IL-10 by peripheral blood lymphocytes in persons with autoimmune thyroiditis.

    Science.gov (United States)

    Kvaratskhelia, E; Dabrundashvili, N; Gagua, M; Maisuradze, E; Mikeladze, D

    2008-11-01

    Human T lymphocytes expose ionotropic and metabotropic glutamate receptors, which control immune responses, cell activation, maturation, and death. Several cytokines release during inflammation which identification may have important physiological and clinical implications. Main biological function of IL-10 is limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells. Various inflammatory molecules regulated the secretion of IL-8 and IL-10, but the action of glutamate on the biosynthesis of cytokines is unknown. We have found that in peripheral blood lymphocytes glutamate at the concentrations within normal plasma levels (1 x 10(-5) M), as well as at lower concentration (0.3 x 10(-6) M) changes the secretion of immunosuppressive cytokine IL-10, whereas synthesis of proinflammatory chemokine, IL-8 did not changed significantly. Moreover, our results have shown that peripheral blood lymphocytes from patients with autoimmune thyroiditis release less IL-10 at both concentration of glutamate than peripheral blood lymphocytes from healthy persons. These data suggest that glutamate decrease the secretion of IL-10 by peripheral blood lymphocytes, especially in patients with autoimmune thyroiditis that may be responsible for prolongation of inflammation.

  16. IL-6 promotes growth and epithelial-mesenchymal transition of CD133+ cells of non-small cell lung cancer.

    Science.gov (United States)

    Lee, Soo Ok; Yang, Xiaodong; Duan, Shanzhou; Tsai, Ying; Strojny, Laura R; Keng, Peter; Chen, Yuhchyau

    2016-02-09

    We examined IL-6 effects on growth, epithelial-mesenchymal transition (EMT) process, and metastatic ability of CD133+ and CD133- cell subpopulations isolated from three non-small cell lung cancer (NSCLC) cell lines: A549, H157, and H1299. We developed IL-6 knocked-down and scramble (sc) control cells of A549 and H157 cell lines by lentiviral infection system, isolated CD133+ and CD133- sub-populations, and investigated the IL-6 role in self-renewal/growth of these cells. IL-6 showed either an inhibitory or lack of effect in modulating growth of CD133- cells depending on intracellular IL-6 levels, but there was higher self-renewal ability of IL-6 expressing CD133+ cells than IL-6 knocked down cells, confirming the promoter role of IL-6 in CD133+ cells growth. We then examined tumor growth of xenografts developed from CD133+ cells of A549IL-6si vs. A549sc cell lines. Consistently, there was retarded growth of tumors developed from A549IL-6si, CD133+ cells compared to tumors originating from A549sc, CD133+ cells. The effect of IL-6 in promoting CD133+ self-renewal was due to hedgehog (Hhg) and Erk signaling pathway activation and higher Bcl-2/Bcl-xL expression. We also investigated whether IL-6 regulates the EMT process of CD133- and CD133+ cells differently. Expression of the EMT/metastasis-associated molecules in IL-6 expressing cells was higher than in IL-6 knocked down cells. Together, we demonstrated dual roles of IL-6 in regulating growth of CD133- and CD133+ subpopulations of lung cancer cells and significant regulation of IL-6 on EMT/metastasis increase in CD133+ cells, not in CD133- cells.

  17. Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: role of IL-6.

    Science.gov (United States)

    Morales-Montor, J; Baig, S; Mitchell, R; Deway, K; Hallal-Calleros, C; Damian, R T

    2001-10-15

    Taenia crassiceps cysticercosis results in an impressive feminization in male mice during chronic infection, characterized by increased serum estradiol levels 100 times their normal values, while those of testosterone and dihydrotestosterone are decreased by 85 and 95% respectively. Concomitantly, the levels of follicle-stimulating hormone and IL-6 are increased 70 and 90 times their normal values in the infected male mice. Since a specific Th1/Th2 shift of the immune response has been previously reported during the chronic infection, and this shift may be associated with the feminization process, we proposed that this shift is induced by immunoendocrine interactions during the disease, and this gives way to a change in the initial resistance to the infection in the male mice, which become as susceptible as female mice. To confirm this hypothesis, we depleted immune system activity in two different ways: total body irradiation and neonatal thymectomy. Our results show that when immune system activity is depleted using either strategy, the male mice do not feminize, and the levels of follicle-stimulating hormone and IL-6 are inhibited. Depletion of IL-6 using IL-6(-/-) knockout mice does not produce the feminization process stated above, while restitution of the IL-6(-/-) knockout, irradiated, and thymectomized mice with murine recombinant IL-6 restores the feminization process. Expression of the IL-6 gene was found only in the testes and spleen of infected animals. Our results illustrate the importance of immunoendocrine interactions during a parasitic disease and show a possible new mechanism of parasite establishment in an initially resistant host.

  18. Prevention of hypovolemic circulatory collapse by IL-6 activated Stat3.

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    Jeffrey A Alten

    Full Text Available Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC. We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS. HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3beta, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients.

  19. IL-6/STAT3 signaling pathway is activated in plasma cell mastitis.

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    Liu, Yang; Zhang, Jian; Zhou, Yu-Hui; Jiang, Yi-Na; Zhang, Wei; Tang, Xiao-Jiang; Ren, Yu; Han, Shui-Ping; Liu, Pei-Jun; Xu, Jing; He, Jian-Jun

    2015-01-01

    Plasma cell mastitis (PCM), a particular type of mastitis, mainly occurs in females at nonpregnant and nonlactating stages. The infiltration of abundant plasma cells and lymphocytes is the hallmark of the disease. The incidence rate of PCM increased gradually and its pathogenesis remained unclear. In this study, we investigated the expression of IL-6/STAT3 signaling pathway, which is vital not only for the differentiation of plasma cells but also for survival of plasma cells and T lymphocytes, in 30 PCM cases, 10 acute mastitis cases and 10 normal breast tissues by immunohistochemical analysis. IL-6 level was significantly higher in PCM patients than in acute mastitis patients or normal group. The positive rate of IL-6 and p-STAT3 staining in PCM samples was 93.3% (28/30) and 70% (21/30), respectively, and there was a significant positive association between IL-6 and p-STAT3 staining (r=0.408, P=0.025). In PCM group, the rate of nipple retraction was 40% (12/30). Significantly higher IL-6 expression was found in PCM patients with nipple retraction than in other PCM patients. However, no significant difference in IL-6 or p-STAT3 staining was detected between PCM patients experiencing recurrence and other PCM patients. In addition, Bcl-2 level was higher in PCM patients than in acute mastitis patients or normal group, but there was no difference in Bcl-2 immunostaining between PCM patients experiencing recurrence and other PCM patients. These indicate that IL-6/STAT3 signaling is activated in PCM and may play an important role in the pathogenesis of PCM.

  20. Role of muscle IL-6 in gender-specific metabolism in mice

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    Fernandez-Perez, Antonio; Mogas, Aina; Giralt, Mercedes; Comes, Gemma; Fernandez-Gayol, Olaya; Vallejo, Mario; Hidalgo, Juan

    2017-01-01

    The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473. The stress response was also studied. Results indicate a relevant role of muscle IL-6 in maintaining energy homeostasis, especially in males. Absence of muscle IL-6 in male mice results in lower core body temperature in the light phase, increased respiratory exchange ratio (RER) both at rest and during exercise, increased expression of TCA cycle marked gene, citrate synthase in muscle, reduced fat storage and decreased body weight and food consumption in response to leptin. In females, muscle IL-6 deficiency increases VO2 and CO2 levels similarly. Also in contrast to males, energy expenditure (EE) measured over 48h reveals a significant elevation in female mice with muscle IL-6 deficiency; moreover, they show a modified response to fasting-refeeding and to restraint stress. The present results contribute to the understanding of the role of muscle IL-6 in male and female mouse metabolism, not only during exercise but also in the basal state and in situations where energy balance is altered. PMID:28319140

  1. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    Science.gov (United States)

    Yee, Leland J.; Im, KyungAh; Borg, Brian; Yang, Huiying; Liang, T. Jake

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) (RR=0.80; 95%C.I.: 0.66– 0.98; p=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95%C.I.: 0.66–0.94; p=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95%C.I.: 0.66–0.94; p=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% C.I.: 0.62–1.0; p=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy. PMID:19387461